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Tasuku Yamamoto,1,2 Keiji Oishi,1 Syuichiro Ohata,1 Yoriyuki Murata,1 Yoshikazu Yamaji,1 Maki Asami-Noyama,1 Nobutaka Edakuni,1 Tomoyuki Kakugawa,3 Tsunahiko Hirano,1 Kazuto Matsunaga1 1Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan; 2Department of Respiratory Medicine, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Yamaguchi, Japan; 3Department of Pulmonology and Gerontology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanCorrespondence: Keiji Oishi, Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan, Tel +81 836 85 3123, Fax +81 836 85 3124, Email ohishk@yamaguchi-u.ac.jpBackground: Reports from Europe and North America suggest that female chronic obstructive pulmonary disease (COPD) patients have a higher symptom burden and mortality than male patients. However, little is known about the management reality of female patients with COPD in Japan.Patients and Methods: We compared the clinical characteristics of female COPD patients with those of male using the cohort of the COPD Assessment in Practice study, which is a cross-sectional multicenter observational study.Results: Of the 1168 patients, 133 (11.4%) were female. A history of never smoking was higher in females than males (p< 0.01). Although there was no difference in age or forced expiratory volume in one second (FEV1) % predicted between the groups, modified medical research council dyspnea scale (mMRC) and number of frequent exacerbators were higher in females (mMRC≥ 2: p< 0.01; number of exacerbations≥ 2: p=0.011). The mean forced vital capacity and FEV1 values in females were lower than those in males (p< 0.0001 and p< 0.0001, respectively). Females were more likely to use long-term oxygen therapy and inhaled corticosteroids than males (p=0.016 and p< 0.01, respectively). The prevalence of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, D (ABCD GOLD 2017 classification), and E (ABE GOLD 2023 classification) was higher in females than in males.Conclusion: The disease burden of female patients with COPD is higher than that of male patients in Japan, suggesting the importance of interventions considering female-dominant features such as lower absolute FVC and FEV1, respiratory failure, and asthma-like conditions.Keywords: chronic obstructive pulmonary disease, exacerbation, subjective symptoms, gender difference, observational study

The association between subjective walking speed and metabolic diseases has received limited attention, particularly in individuals with obesity. We aimed to clarify this association using comprehensive health checkup data of participants with obesity. In total, 8578 individuals with a body mass index ≥ 25.0 kg/m 2 , 9626 individuals with waist circumference ≥ 85 cm in men and ≥ 90 cm in women, and 6742 individuals who met both criteria of body mass index and waist circumference were included in this cross-sectional analysis. Subjective walking speed was investigated using the question "Is your walking speed faster than the speed of those of your age and sex?" in a health examination questionnaire. Metabolic diseases were defined according to the guidelines for each disease, and modified Poisson regression analyses were performed. In the model adjusted for age and sex, individuals with obesity based on body mass index and fast subjective walking speed showed significantly lower risk of diabetes mellitus (risk ratio [RR] 0.70; 95% CI 0.63-0.77) and dyslipidemia (RR 0.97; 95% CI 0.94-1.00). Similarly, among those with obesity based on waist circumference and both body mass index and waist circumference, fast subjective walking speed showed a significant negative association with hypertension (RR 0.94; 95% CI 0.90-0.97 and RR 0.95; 95% CI 0.92-0.99, respectively), diabetes mellitus (RR 0.70; 95% CI 0.64-0.77 and RR 0.70; 95% CI 0.63-0.77, respectively), and dyslipidemia (RR 0.96; 95% CI 0.94-0.99 and RR 0.96; 95% CI 0.94-0.99, respectively). Thus, among individuals with obesity, the odds of metabolic diseases were lower if their subjective walking speed was fast. This study contributes to earlier prevention of the cascade of diseases that begin with obesity., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Simultaneous closure of the left atrial appendage (LAA) during cardiac procedures has become a common preventive measure against cardiogenic embolic events associated with atrial fibrillation. However, this strategy encounters limitations during minimally invasive mitral valve surgery through a right minithoracotomy because access to the LAA is limited. The use of endocardial sutures for surgical exclusion of the LAA is also well established but has a notable rate of closure failure. We introduced a new surgical LAA closure technique called the inverted spiral closure technique (ISCT)., Methods: Between July 2020 and August 2021, 26 patients underwent LAA closure with ISCT concomitant to mitral valve surgery in our hospital. Early postoperative outcomes and any stroke or thromboembolic event during the follow-up were evaluated. Transthoracic or transesophageal echocardiography (TEE) was used to assess LAA patency., Results: The ISCT procedure was performed successfully in all cases. No significant persistent flow between the left atrium and LAA was observed on intraoperative TEE. During a median follow-up of 1.1 years, no patients experienced stroke, myocardial infarction, or death. Postoperative echocardiography showed no significant residual flow within the LAA. One patient was incidentally found to have recanalization between the left atrium and LAA several months after surgery on an enhanced computed tomography scan during coronary evaluation., Conclusions: The ISCT can be performed reliably through the same left atriotomy for mitral valve surgery and is a useful and effective technique for surgical LAA exclusion. There are still not enough patients and modalities for postoperative evaluation., 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.

Background: Clinical remission (CR) is a new realistic management goal for patients with asthma, regardless of the disease severity., Objective: To investigate the rate of achievement of CR in patients treated with inhaled corticosteroid/long-acting β 2 -agonist (ICS/LABA) and nonbiologics and the characteristics of patients who achieved CR., Methods: We performed a post hoc analysis from a multicenter, cross-sectional survey in Japan. 3-way CR was defined as the absence of exacerbation, no use of maintenance oral corticosteroids, and the absence of significant asthma symptoms (5-item Asthma Control Questionnaire < 1.5). We defined 4-way CR as 3-way CR plus having normalized lung function (forced expiratory volume in 1 second [%FEV 1 ] ≥ 80%). Deep remission was defined as 4-way CR plus suppressed type 2 airway inflammation (fraction of exhaled nitric oxide [FeNO] < 35 ppb)., Results: The criteria for 3-way CR, 4-way CR, and deep remission were met by 56.9%, 35.0%, and 24.7% of patients, respectively. Compared with patients who achieved the 3-way CR, unachieved patients have lower %FEV 1 (77.6% vs 85.4%; P < .0001) and higher FeNO levels (42 ppb vs 34 ppb; P = .0182), and there were more discordances in asthma control perception between patient and physicians (38.5% vs 9.3%; P < .0001). Physician-patient discordance was an independent factor that prevented the achievement of the 3-way CR in the logistic regression analysis, even when adjusted for %FEV 1 and FeNO (odds ratio 0.397; P < 0.0001)., Conclusions: Achieving CR in patients treated with ICS/LABA without biologics is challenging. Discrepancies between patient and physician perceptions on asthma control are significant barriers to achieving CR., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

This study introduces OpenMAP-T1, a deep-learning-based method for rapid and accurate whole-brain parcellation in T1- weighted brain MRI, which aims to overcome the limitations of conventional normalization-to-atlas-based approaches and multi-atlas label-fusion (MALF) techniques. Brain image parcellation is a fundamental process in neuroscientific and clinical research, enabling a detailed analysis of specific cerebral regions. Normalization-to-atlas-based methods have been employed for this task, but they face limitations due to variations in brain morphology, especially in pathological conditions. The MALF techniques improved the accuracy of the image parcellation and robustness to variations in brain morphology, but at the cost of high computational demand that requires a lengthy processing time. OpenMAP-T1 integrates several convolutional neural network models across six phases: preprocessing; cropping; skull-stripping; parcellation; hemisphere segmentation; and final merging. This process involves standardizing MRI images, isolating the brain tissue, and parcellating it into 280 anatomical structures that cover the whole brain, including detailed gray and white matter structures, while simplifying the parcellation processes and incorporating robust training to handle various scan types and conditions. The OpenMAP-T1 was validated on the Johns Hopkins University atlas library and eight available open resources, including real-world clinical images, and the demonstration of robustness across different datasets with variations in scanner types, magnetic field strengths, and image processing techniques, such as defacing. Compared with existing methods, OpenMAP-T1 significantly reduced the processing time per image from several hours to less than 90 s without compromising accuracy. It was particularly effective in handling images with intensity inhomogeneity and varying head positions, conditions commonly seen in clinical settings. The adaptability of OpenMAP-T1 to a wide range of MRI datasets and its robustness to various scan conditions highlight its potential as a versatile tool in neuroimaging., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Increasing expectations that biologics can be used as disease-modifying agents have introduced the concept of clinical remission (CR) in managements of severe asthma. Given the clinical relevance of computed tomography (CT) and blood biomarkers, we hypothesized that further refinement of CR criteria as well as incorporation of CT and blood biomarkers as indicators for structural and biological remission (SR, BR) would enable predicting long-term disease stability in patients with severe asthma treated with biologics., Methods: This Japanese multicenter prospective observational cohort will enroll patients with severe asthma who will start a new biologic (including a change from another biologic). The enrolled patients will be longitudinally followed up for 3 years. At enrollment, patients will undergo postbronchodilator spirometry, blood tests, fractional exhaled nitric oxide, chest and sinus CT, and patient-reported outcome questionnaires. Follow-up examinations will be performed at 1, 3, 6, 12, 24, and 36 months. The rates of CR resulting from different criteria after 1 year of treatment with biologics will be compared, and factors associated with long-term disease stability after 3 years of biologic treatments will be identified., Discussion: This multicenter study in Japan will provide data that will help establish more appropriate criteria for CR, structural remission, and biological remission to predict long-term disease stability in patients with severe asthma who receive biologic therapy., Ethics and Dissemination: The study was approved by the Ethics Committee of Kyoto University (No. R4419, approval date June 11th, 2024)., Trial Registration: The University Hospital Medical Information Network (UMIN000053771)., Competing Interests: Declaration of competing interest N.T. received honoraria for lectures for AstraZeneca and research funding from Fujifilm, and Daiichi Sankyo. Y.H. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi, Boehringer Ingelheim JP. S.M. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi. J.M. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi and research funding from AstraZeneca, GlaxoSmithKline, Novartis. T.W. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi. K.O. received honoraria for lectures for AstraZeneca, Boehringer Ingelheim JP. M.Y. received honoraria for lectures for AstraZeneca, GlaxoSmithKline and research funding from Boehringer Ingelheim JP, GlaxoSmithKline, Clairvo technologies Inc. K.A. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim JP. Y.N. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim JP and research funding from Boehringer Ingelheim JP, GlaxoSmithKline, Clairvo technologies Inc. T. Hirano received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi. K. Matsunaga received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Kyorin Pharma, Novartis, Sanofi. T. Koya received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi, Novartis. H.M. received honoraria for lectures for AstraZeneca, Sanofi, GlaxoSmithKline, Novartis. K.F. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi, Novartis, Boehringer Ingelheim JP, Kyorin Pharma and research funding from AstraZeneca, GlaxoSmithKline, Novartis, Boehringer Ingelheim JP, Chugai Pharmaceutical. S. K. received honoraria for lectures for AstraZeneca, Boehringer Ingelheim JP and research funding from Novartis. T. Kaneko received honoraria for lectures for AstraZeneca, Kyorin Pharma, Novartis, Sanofi, Boehringer Ingelheim JP. T. Hirai. received research funding from Fujifilm and Daiichi Sankyo., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background/aim: Sarcopenia is diagnosed based on grip strength and skeletal muscle mass. Although decreased skeletal muscle mass has been reported to be associated with poor outcomes after hepatectomy, a few studies have included data on grip strength in hepatectomy candidates. This multicenter study investigated the clinical factors and postoperative complications associated with sarcopenia by assessing the grip strength and skeletal muscle mass in patients undergoing hepatectomy for hepatocellular carcinoma (HCC)., Patients and Methods: Data from patients who underwent hepatectomy for HCC between January 2020 and March 2022 were retrospectively collected from multi-institutional databases. Sarcopenia was defined as reduced grip strength and skeletal muscle mass. The patients were categorized into the sarcopenia and non-sarcopenia groups, and baseline characteristics and short term outcomes were compared between the two groups., Results: Overall, 253 patients were included, among which 36 (14.2%) had sarcopenia. The sarcopenia group was significantly associated with older age, low body mass index, comorbid heart or chronic pulmonary disease, cerebrovascular accident history, and overall and major postoperative complications compared to the non-sarcopenia group. Among major postoperative complications [Clavien-Dindo classification (CDC) ≥III], the incidence of bile leakage and intra-abdominal abscess were higher in the sarcopenia group than in the non-sarcopenia group. Multivariate analysis revealed that sarcopenia was an independent risk factor for overall and major postoperative complications (CDC ≥III)., Conclusion: Sarcopenia, defined by grip strength and skeletal muscle mass, is a predictor of overall and major complications after hepatectomy for HCC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The efficacy of antifibrotic agents in idiopathic pulmonary fibrosis (IPF) has been demonstrated and early introduction is recommended, especially in patients with preserved performance status (PS). We aimed to determine the proportion of untreated IPF cases using real-world data and to assess the factors associated with non-intervention., Methods: A prospective observational study using questionnaires was performed on 518 patients with interstitial lung disease (ILD) and their attending physicians who visited a clinic, general hospital, or tertiary respiratory center between December 2019 and October 2020. Patients responded with subjective symptoms and PS, whereas physicians responded with diagnosis, treatment, and reasons for their treatment choices. Principal component analysis (PCA) was performed using age, sex, BMI, medical facility, specialized tests, and symptom severity., Results: We included 207 patients with IPF. Among them, 168 has a good PS (≤2), which could be indicative of treatment; 130 (77.4%) were not treated with antifibrotic agents. The PCA revealed a trend consistent with that of antifibrotic agent therapy and the distribution of medical facilities, with a treatment intervention rate of 16% in general hospitals and 62% in tertiary respiratory centers. In general hospitals, low symptom severity (PS, mMRC, and no use of long-term oxygen therapy) was a relevant factor for non-intervention with antifibrotic agents (p < 0.001)., Conclusion: Antifibrotic treatment interventions varied by facility in cases with good PS. Patients with milder symptoms are not being treated early in general hospitals and more collaboration between general hospitals and specialized facilities is necessary., Competing Interests: Declaration of competing interest M.A. (Maki Asami-Noyama) received subsidies from Nippon Boehringer Ingelheim Co., Ltd. The other authors have no conflicts of interests., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

Case 1: A 71-year-old man was admitted to our hospital with progressive fever and dyspnea, which had developed three days after the onset of COVID-19. Initial chest computed tomography (CT) revealed a pulmonary lesion consistent with a secondary bacterial infection. Streptococcus pyogenes was isolated from cultures of primary sputum collected from the endotracheal tube, and identified as the causative microorganism. Case 2: A 91-year-old man was transferred to our hospital with severe hypotension, which had developed nine days after the onset of COVID-19. A chest CT revealed pericardial effusion and pericardiocentesis yielded purulent fluid. S. pyogenes was isolated from the fluid specimens and was identified as the causative microorganism of the secondary bacterial pericarditis. Isolates from both patients were subsequently identified as M1 UK -lineage S. pyogenes via genetic analysis. This report implicates COVID-19 as a potential risk factor for severe M1 UK infection via the respiratory tract., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Physiologic knee kinematics is crucial for successful total knee arthroplasty (TKA) but are often not replicated. Using a medial stabilizing technique (MST) minimizes bone resection but results in lateral laxity. This study aimed to investigate the effects of lateral laxity on knee kinematics and symptoms after TKA., Methods: Mobile-bearing cruciate-retaining MST-TKA was performed on 40 knees using a navigation system. In the kinematic analysis, the anteroposterior (AP) translations of the medial femoral condyle (MFC) and lateral femoral condyle (LFC), femoral rotation angles, and medial and lateral component gaps were recorded every 0.1 ​s. These data were extracted from the software from 0° to 120° flexion in 10° increments. Kinematics was classified as the medial center of rotation (MCR) or non-MCR between 0° to 90° of flexion. Lateral laxity was calculated by subtracting the medial component gap from the lateral component gap. The final follow-up Knee Injury and Osteoarthritis Outcome Scores (KOOS) were evaluated. The relationships between the pre- and post-operative kinematics and between postoperative lateral laxity and kinematics were assessed using Spearman's correlation coefficients. Finally, the correlation between postoperative lateral laxity and KOOS symptoms was evaluated using linear regression analysis., Results: Preoperative kinematics, including AP translation of the MFC and LFC and femoral rotation, correlated with postoperative kinematics (all P ​< ​0.001). Additionally, postoperative lateral laxity correlated with postoperative AP translation of the MFC, LFC, and femoral rotation (all P ​< ​0.001). Furthermore, the receiver operating characteristic analysis indicated a cutoff value of 0.9 ​mm on postoperative lateral laxity at 90° flexion for postoperative MCR (P ​< ​0.001). Postoperative lateral laxity at 90° flexion was significantly correlated with KOOS symptoms (β ​= ​0.465, P ​= ​0.025)., Conclusion: Preoperative kinematics and postoperative lateral laxity correlated with postoperative kinematics after MST-TKA. Postoperative lateral laxity greater than 0.9 ​mm at 90° flexion was associated with physiological kinematic motion, leading to fewer knee symptoms in the PROMs. The key to successful TKA was considered to be keeping the asymmetric gap balance with physiological lateral laxity, rather than the conventional symmetrical gap balance., Level of Evidence Level Iii: Retrospective study., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Spermatogenesis requires a large amount of energy, which is primarily produced by the mitochondrial electron transfer chain. Mitochondrial dysfunction affects male infertility, suggesting a relationship between the electron transfer chain and male infertility. COXFA4L3 (C15ORF48) is an emerging subunit protein of cytochrome oxidase specifically expressed in germ cells during spermatogenesis, and it may be involved in male infertility. Therefore, to investigate whether COXFA4L3 could be a marker of mitochondrial dysfunction in the sperm, this study examined the protein expression and localization profile of COXFA4L3 in the sperm of male patients with infertility., Methods: Twenty-seven semen samples from a male infertility clinic at the Reproductive Center of Yokohama City University Medical Center were used to analyze sperm quality parameters and the expression and localization of energy production-related proteins. These data were compared with the outcomes of infertility treatment., Results: The expression levels of COXFA4L3 varied significantly between samples. Furthermore, COXFA4L3 was ectopically localized to the acrosome., Conclusions: Ectopic expression of COXFA4L3 and PNA-stained acrosomes may be useful parameters for fertility treatment selection. Assessing the acrosomal localization of COXFA4L3 will expedite pregnancy treatment planning., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

The association of posterior thalamic strokes with the presence of chronic 'thalamic' pain, was described in the early 1900s and revisited in a recent review of these patients. Acute pain in corporal structures is associated with the spinothalamic tract (STT) which originates in the dorsal horn of the spinal cord, while that associated with cranial structures is associated with the spinal division of the trigeminal nucleus. These pathways terminate in the ventral posterior nucleus (VP) including its posterior and inferior subnuclei, and its core which is classically associated with tactile and haptic functions. In medial nuclei (medial dorsal and intralaminar) receptive fields are large and stimulation evokes diffuse unpleasant sensations and pain while neurons in these nuclei subserve cognitive processes of attention, alerting, and conditioning. In the lateral nuclei neurons have small receptive and projected fields and high resolution of responses to somatic stimuli. Neurons in the lateral nuclei respond to stimuli producing pain, temperature, and visceral sensations while stimulation evokes similar sensations. Small strokes in VP core versus structures located inferior and posterior are associated with 'thalamic' pain and decreased tactile, painful and cold sensations, and with decreased evoked potentials for painful (laser) heat and median nerve stimulation (electrical). Lesions of VP, but not Vmpo, are associated with 'thalamic' pain, contrary to the recent 'disinhibition' model. We review the evidence that the lateral nuclei are associated with multiple processes including tactile, nociceptive, visceral and thermal content of stimuli, while the medial nuclei are related to cognitions about those stimuli.

Introduction: Daily torpor is an active hypothermic phenomenon that is observed in some mammals and birds during fasting. A decrease in blood pressure has also been observed in torpor; however, there remains a lack of knowledge of the underlying mechanism. We have previously reported that ghrelin, an orexigenic hormone, has a hypothermic effect and is essential for the induction and maintenance of torpor. It is also known that the ghrelin secretion is enhanced during fasting and that ghrelin receptors are distributed in the cardiovascular system. Therefore, this study was conducted to test the hypothesis that ghrelin is actively involved in the regulation of blood pressure during torpor induction., Methods: Male wild-type and ghrelin gene-deficient mice were generated by homologous recombination as previously reported. Mice, 10 weeks old, were included in this study and housed five per cage. The mice were maintained on a 12-h light/dark cycle (lights on from 7:00 to 19:00) with access to food and water ad libitum., Results: The continuous measurement of blood pressure using a telemetry system showed that induction of torpor by fasting did not decrease blood pressure in ghrelin gene-deficient mice. The analysis of heart rate variability revealed that sympathetic nerve activity was predominant in ghrelin-deficient mice during fasting. Furthermore, these features were cancelled by administration of a ghrelin receptor agonist and were comparable to those in wild-type mice., Discussion: In this study, we showed that blood pressure was elevated in ghrl -/- mice and that the blood pressure rhythm was abnormal. Furthermore, we showed that the ghrelin gene deficiency does not cause sufficient blood pressure reduction upon entry into the torpor, and that the administration of the ghrelin receptor agonist, GHRP-6, causes blood pressure reduction associated with torpor. Thus, we have shown for the first time that the active role of ghrelin is essential for active blood pressure reduction associated with torpor, and that this action is mediated by the inhibition of sympathetic nerve activity by ghrelin., 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 Matsui, Ida, Oishi, Kojima and Sato.)

Residents in nursing homes face heightened COVID-19 risks. We aimed to assess the adverse events (AEs) rates and antibody responses after the first to the fifth dose of COVID-19 mRNA vaccination in a nursing home cohort. Ninety-five SARS-CoV-2 naïve participants consisted of 26 staff (median age, 51 years) and 69 residents (median age, 88 years). Life-threatening AEs were reported in neither residents nor staff. The severity of non-life-threatening AEs was graded, and severe AEs were reported only in staff. The AEs rates were considerably lower in residents, compared to those in staff. Anti-RBD IgG and the neutralizing titers (NTs) against Wuhan and Omicron BA.4/BA.5 did not differ significantly between those with 'any AE' and 'no AE' among both staff and residents two months after the second, third and fifth doses, while the anti-RBD IgG significantly differed between two groups after third dose in residents. These findings suggest that the anti-RBD IgG and the NTs increase regardless of the occurrence of AEs. Our study underscores a robust antibody response in both in staff and residents, and fewer AEs following COVID-19 vaccination in SARS-CoV-2 naïve residents than staff, supporting the recommendation for mRNA booster doses in older adults at high-risk care facilities., (© 2024. The Author(s).)

Importance: It remains unclear which risk factors accelerate brain atrophy along with a progression from normal cognition to mild cognitive impairment (MCI)., Objective: To examine risk factors associated with the acceleration of brain atrophy and progression from normal cognition to MCI based on long-term longitudinal data for middle-aged and older adults., Design, Setting, and Participants: Data for this cohort study were extracted from the Biomarkers for Older Controls at Risk for Dementia (BIOCARD) cohort, initiated at the National Institutes of Health from January 1, 1995, to December 31, 2005, and continued at Johns Hopkins University from January 1, 2015, to October 31, 2023. All participants were cognitively normal at baseline. The participants whose structural magnetic brain imaging (MRI) of the brain and cerebrospinal fluid (CSF) measures were available for over 10 years were included., Exposures: Longitudinal structural MRI of the brain and measurement of CSF biomarkers for Alzheimer disease pathology (ratio of amyloid β peptide 42 [Aβ42] to Aβ40, tau phosphorylated at threonine 181, and total tau)., Main Outcomes and Measures: Annual change rates of segmental brain volumes, Kaplan-Meier survival curves plotting time to event for progression to MCI symptom onset, and hazard ratios (HRs) determined by Cox proportional hazards regression models., Results: A total of 185 participants (mean [SD] age, 55.4 [8.4] years; 116 women [63%]) were included and followed up for a maximum of 27 years (median, 20 [IQR, 18-22] years). The groups with high levels of atrophy in the white matter and enlargement in the ventricles had an earlier progression from normal cognition to MCI symptom onset (HR for white matter, 1.86 [95% CI, 1.24-2.49]; P = .001; HR for ventricles, 1.71 [95% CI, 1.19-2.24]; P = .009). Diabetes was associated with progression to MCI (HR, 1.41 [95% CI, 1.06-1.76]; P = .04), as was a low CSF Aβ42:Aβ40 ratio (HR, 1.48 [95% CI, 1.09-1.88]; P = .04), and their combination had a higher HR of 1.55 (95% CI, 1.13-1.98]; P = .03), indicating a synergic association of diabetes and amyloid pathology with MCI progression., Conclusions and Relevance: In this cohort study of middle-aged and older adults, higher rates of volume change in the white matter and ventricles, along with the presence of diabetes and a low CSF Aβ42:Aβ40 ratio, were identified as important risk factors for the progression to MCI. These results support the importance of identifying individuals who have accelerated brain atrophy to optimize preventive strategies for progression to MCI.

Background: Severe acute cholecystitis (AC) is a challenging disease because it comprises coexisting systemic infections that lead to vital organ dysfunction. This study evaluated the optimal surgical timing and efficacy of preoperative percutaneous cholecystostomy (PC) for patients with severe AC., Methods: Data of 142 patients who underwent cholecystectomy for severe AC between 2011 and 2021 were retrospectively collected from the multi-institutional database of the Hiroshima Surgical Study Group of Clinical Oncology. Patients were divided into the early cholecystectomy (EC) group (within 72 h of symptom onset) and delayed cholecystectomy (DC) group. They were also subdivided into the upfront cholecystectomy group and preoperative PC before cholecystectomy group. The diagnosis and severity of AC were graded according to the Tokyo Guidelines 2018. Clinicopathological variables and outcomes were compared., Results: No significant differences in age, body mass index, American Society of Anesthesiologists (ASA) classification, and Charlson comorbidity index between the EC and DC groups were observed. Preoperative drainage was more commonly performed for the DC group than for the EC group. Local severe AC features were more commonly detected in the DC group than in the EC group. The postoperative outcomes of the EC and DC groups were comparable. Compared to the PC before cholecystectomy group, the upfront cholecystectomy group included more patients with ASA physical status ≥ 3 and more patients who used oral warfarin. Warfarin usage and cardiovascular dysfunction rates of the PC after cholecystectomy group were higher than those of the upfront cholecystectomy group. PC was associated with significantly less intraoperative bleeding and shorter hospital stays., Conclusions: Patients who can tolerate general anesthesia are good candidates for EC. Patients who use warfarin and those with cardiovascular dysfunction are considered to be at high risk for postoperative complications; therefore, to prevent AC recurrence during the waiting period, PC before cholecystectomy during the same admission is more appropriate than upfront cholecystectomy for these patients., (© 2024. The Author(s).)

Introduction: The American Society of Anesthesiologists (ASA) classification is used to assess the fitness of a patient for surgery. Whether laparoscopic surgery is appropriate for colorectal cancer patients with poor ASA performance status (PS) remains unclear., Methods: Among 4585 patients who underwent colorectal surgery between 2016 and 2023, this study retrospectively reviewed all 458 patients with ASA-PS ≥3. Patients were divided into two groups: patients treated by open surgery (O group, n = 80); and patients treated by laparoscopic surgery (L group, n = 378). We investigated the impact of surgical approach on postoperative complications in patients with colorectal cancer and ASA-PS ≥3., Results: Operation time was longer (170 min vs. 233 min, p < .001), blood loss was less (156 mL vs. 23 mL, p < .001), postoperative complications were less frequent (40.0% vs. 25.1%, p = .008), and hospital stay was shorter (23 days vs. 14 days, p < .001) in L group. Univariate analysis revealed rectal cancer, open surgery, longer operation time, and blood loss as factors significantly associated with postoperative complications. Multivariate analysis revealed open surgery (odds ratio [OR] 2.100, 95% confidence interval [CI] 1.164-3.788; p = .013) and longer operation time (OR 1.747, 95% CI 1.098-2.778; p = .018) as independent predictors of postoperative complications., Conclusion: Laparoscopic surgery provides favorable outcomes for colorectal cancer patients with poor ASA-PS., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Objectives: Tracheal regeneration is challenging owing to its unique anatomy and low blood supply. Most tracheal regeneration applications require scaffolds. Herein, we developed bio-three-dimensional-printed scaffold-free artificial tracheas., Methods: We fabricated bio-three-dimensional-printed artificial tracheas. Their anterior surface comprised hyaline cartilage differentiated from mesenchymal stem cells, and their posterior surface comprised smooth muscle. Human bone marrow-derived mesenchymal stem cells were cultured and differentiated into chondrocytes using fibroblast growth factor-2 and transforming growth factor-beta-3. Initially, horseshoe-shaped spheroids were printed to cover the anterior surface of the artificial trachea, followed by the application of human bronchial smooth muscle cells for the posterior surface. After a 3-week maturing process, the artificial trachea was subjected to histological and immunohistochemical analyses., Results: The anterior surface of the artificial trachea comprised well-differentiated hyaline cartilage from human bone marrow-derived mesenchymal stem cells. Immunohistochemistry revealed that the smooth muscle expressed α-smooth muscle actin and smooth muscle myosin heavy chain 11., Conclusions: A bio-three-dimensional-printed scaffold-free artificial trachea comprising different tissues at the front and back was successfully fabricated., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Clostridium perfringens, which produces C. perfringens enterotoxin (CPE), is a major causative agent of food poisoning owing to its gastrointestinal symptoms. Genotyping is important for identifying the etiological agent in outbreaks of C. perfringens. We attempted to genotype strains isolated from an outbreak of food poisoning in Toyama in 2023 using single nucleotide polymorphism (SNP) analysis. The strains of C. perfringens were isolated from a piece of curry food consumed by all patients and from the feces of the patients and employees. The cpe gene was detected in isolates from patients and curry food. The cpe-negative isolates were found in patients who consumed curry foods and in employees. The results of the SNP analysis suggest that the patient- and curry-derived isolates were likely from the same source but were unlikely to be related to the employee-derived isolates. The results of the SNP and pulsed-field gel electrophoresis (PFGE) analyses were consistent, indicating that the patient- and curry-derived isolates came from the same source. SNP analysis, a whole-genome-based genotyping method, is a promising alternative to the traditional PFGE method. Further studies are needed to accumulate more experience with genotyping using SNP analysis for the epidemiological investigation of outbreaks of C. perfringens.

Background: Hepatocellular carcinoma (HCC) ranks third in cancer-related deaths globally. Despite treatment advances, high post-hepatectomy recurrence rates (RR), especially with liver fibrosis and hepatitis C virus infection, remain challenging. Key prognostic factors include vascular invasion and perioperative blood loss, impacting extrahepatic recurrence. Natural killer (NK) cells are crucial in countering circulating tumor cells through TRAIL-mediated pathways. The aim of this study was to validate the liver immune status index (LISI) as a predictive tool for liver NK cell antitumor efficiency, particularly in HCC patients with vascular invasion., Methods: A retrospective analysis of 1337 primary HCC hepatectomies was conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). Clinicodemographic data were extracted from electronic medical records. Prognostic indices (FIB-4, ALBI, ALICE, GNRI, APRI, and LISI) were evaluated using area under the receiver operating characteristic curve values. Survival analyses employed Kaplan-Meier estimations and log-rank tests., Results: LISI significantly correlated with other prognostic markers and stratified patients into risk groups with distinct overall survival (OS) and RR. It showed superior predictive performance for 2-year OS and RR, especially in patients with vascular invasion. Over longer periods, APRI and FIB-4 index reliabilities improved. The HISCO-HCC score, combining LISI, tumor burden score, and alpha-fetoprotein levels, enhanced prognostic accuracy., Conclusion: LISI outperformed existing models, particularly in HCC with vascular invasion. The HISCO-HCC score offers improved prognostic precision, guiding immunotherapeutic strategies and individualized patient care in HCC., (© 2024 The Author(s). Journal of Hepato‐Biliary‐Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

We have previously reported a clinical case in which a hospitalized patient with a history of hematopoietic stem cell transplantation for acute myeloid leukemia was persistently infected with SARS-CoV-2. This study investigated the neutralizing activity of patient sera against cultured viruses isolated at each time point. We also continued to decipher and analyze the whole-genome sequence of the virus. The results showed that the neutralizing activity against the cultured virus at each time point was higher in the sera collected in the late stage of infection. However, the cultured virus collected in the late stage of infection was less likely to be neutralized not only by the sera collected in the early stage of infection but also by the sera collected in the late stage. Moreover, the virus mutated in a manner that allowed it to escape neutralizing antibodies in a host vulnerable to prolonged infection, such as immunocompromised patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

tDCS modulates the activity of the neuronal networks to induce the desired behavioural changes. Two factors determine its effectiveness- (1) whether the network being stimulated is relevant to the task, and (2) if there is a scope for improvement in behavioral performance. To explore this, both dorsal (sub-lexical) and ventral (lexical) reading networks were stimulated (20 min, 2 mA) in 25 healthy young volunteers. Participants performed two reading tasks with different levels of lexical involvement: word fragment completion tasks (WCT) and word association tasks (WAT), while event-related potentials (ERPs) were recorded simultaneously. The study used a within-subject design over three sessions, comparing various electrode montages targeting the dorsal pathway's left inferior parietal lobule or the ventral reading pathway's left middle temporal lobule, as well as sham stimulation. The impact of tDCS sessions (dorsal, ventral, & sham) and task type (WCT & WAT) on priming effects (primed vs. unprimed) of behavioral performance (accuracy and reaction times), and ERP parameters (N400 amplitudes and latencies) were statistically analyzed.It was found that tDCS modulated the performance of WAT only (a task with a lower priming effect). The failure to modulate WCT (larger priming effect) indicated that tDCS was effective for conditions with room for improvement compared to a task where performance has reached the ceiling. Ventral stimulation enhanced accuracy in the WAT condition and shortened the N400 latency of the priming effect. In contrast, dorsal stimulation delayed the priming effect reaction time in the WAT condition and enhanced the N400 amplitude. To conclude, enhancement in performance due to tDCS occurs when the network (ventral) being stimulated aligns with the cognitive demands of the task and there is a scope for improvement., (© 2024. The Author(s).)

Purpose: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel score that offers a good reflection of nutritional status, inflammatory response, and immune system status. The CALLY index is reported to correlate with the prognosis of various carcinomas. The purpose of the present study was to investigate the association between the CALLY index and the short-term prognosis of obstructive colorectal cancer managed with a colonic stent., Methods: The subjects of this retrospective study were 263 patients who underwent colorectal resection after colonic stenting for obstructive colorectal cancer between 2016 and 2023. Patients were classified into a group with a low CALLY index (CALLY-L group, n = 85) and a group with a high (CALLY-H group, n = 178) CALLY index., Results: The CALLY-L group had greater blood loss (53 mL vs 20 mL, p = 0.002) and higher poor performance status (PS3; 20% vs 10.1%, p = 0.033), open surgery (21.2% vs 7.3%, p = 0.001), distant metastases (41.2% vs 20.8%, p = 0.01), and postoperative complications (30.6% vs. 18.5%, p = 0.039) than the CALLY-H group. Multivariate analysis identified a prolonged operative time (odds ratio 1.983, 95% confidence interval 1.013-3.881; p = 0.045), greater blood loss (odds ratio 2.572, 95% confidence interval 1.291-5.129; p = 0.007) and a low CALLY index (odds ratio 1.961, 95% confidence interval 1.013-3.795; p = 0.045) as independent predictors of complications., Conclusion: The CALLY index may be a useful predictor of postoperative complications of obstructive colorectal cancer., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Although endoscopic sinus surgery (ESS) is beneficial in improving asthma symptoms, its impact on the lung function in patients with asthma and chronic rhinosinusitis remains unclear. We herein report a case of severe asthma with eosinophilic chronic rhinosinusitis, in which ESS substantially improved airflow limitation and concomitantly reduced fractional exhaled nitric oxide and blood eosinophil counts. ESS likely relieved airflow limitation by suppressing type 2 inflammatory pathways. This case highlights ESS as a promising strategy for achieving clinical remission in patients with severe asthma and chronic rhinosinusitis.

Pigs are the most common amplifying hosts of the Japanese encephalitis virus (JEV). In 2016, four residents on Tsushima Island who did not own pig farms were diagnosed with JE. Therefore, a serosurvey was conducted to estimate the risk and seroprevalence of JEV after the outbreak. Sera collected from 560 Tsushima Island residents between January and September 2017 were tested for neutralizing antibodies against JEV strains JaGAr01 (genotype 3) and Muar (genotype 5). Sera collected from six wild boars between June and July 2022 were tested. The seroprevalence rates of neutralizing antibodies against JaGAr01 and Muar were 38.8% and 24.6%, respectively. High anti-JEV neutralizing antibody titers of ≥320 were identified in 16 residents, including 3 younger than 6 years with prior JEV vaccination, 2 in their 40s, and 11 older than 70. However, no anti-JEV-specific IgM was detected. Residents who engaged in outdoor activities had higher anti-JEV antibody titers. Sera from wild boars were negative for JEV RNA, but four of six samples contained neutralizing antibodies against JEV. Therefore, JEV transmission continues on Tsushima Island, even in the absence of pig farms, and wild boars might serve as the amplifying hosts.

Background: Goblet cell carcinoid (GCC) of the appendix is a rare tumor characterized by neuroendocrine and adenocarcinoma features. Accurate preoperative diagnosis is very difficult, with most patients complaining mainly of abdominal pain. Computed tomography shows swelling of the appendix, so diagnosis is usually made incidentally after appendectomy based on a preoperative diagnosis of appendicitis. Even if a patient undergoes preoperative colonoscopy, accurate endoscopic diagnosis is very difficult because GCC shows a submucosal growth pattern with invasion of the appendiceal wall., Case Summary: Between 2017 and 2022, 6 patients with GCC were treated in our hospital. The presenting complaint for 5 of these 6 patients was abdominal pain. All 5 patients underwent appendectomy, including 4 for a preoperative diagnosis of appendicitis and the other for diagnosis and treatment of an appendiceal tumor. The sixth patient presented with vomiting and underwent ileocecal resection for GCC diagnosed from preoperative biopsy. Although 2 patients with GCC underwent colonoscopy, no neoplastic changes were identified. Two of the six patients showed lymph node metastasis on pathological examination. As of the last follow-up (median: 15 mo), all cases remained alive without recurrence., Conclusion: As preoperative diagnosis of GCC is difficult, this possibility must be considered during surgical treatments for presumptive appendicitis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In this study, we evaluated the thermal environments of different tennis courts using wet-bulb globe temperature (WBGT) meters. WBGT meters were installed in an outdoor hard court, sand-filled artificial grass court, and clay court (a softball field), and measurements were taken hourly from 9:00 to 17:00 on weekdays from June 1 to September 21, 2022. The results were compared with data from different courts and the nearest Japan Meteorological Agency station (JMA WBGT) based on the Japan Sports Association's guidelines for exercise to prevent heat stroke. The median WBGT on each court was significantly higher for hard courts at the "Warning" (25 ≤ JMA WBGT < 28) level or above, sand-filled artificial grass courts at the "Severe Warning" (28 ≤ JMA WBGT < 31) level or above, and clay courts at the "Danger" (31 ≤ JMA WBGT) level than the JMA WBGT. Compared with the JMA WBGT, hard and sand-filled artificial grass courts are played on under particularly hot conditions. The results of this study could indicate to tournament organizers and coaches the importance of measuring the WBGT on each court surface from an early stage to prevent heat-related incidents., (© 2024. The Author(s).)

Background: The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, a 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific PBMC responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. Cellular immune responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants., Results: LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not., Conclusions: Older and severely frail individuals may exhibit diminished spike-specific PBMC responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that in the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation., (© 2024. The Author(s).)

Background/Objectives : COPD patients who are frail have been reported to develop brain atrophy, but no non-invasive diagnostic tool has been developed to detect this condition. Our study aimed to explore the diagnostic utility of the Kihon Checklist (KCL), a frailty questionnaire, in assessing hippocampal volume loss in patients with COPD. Methods : We recruited 40 COPD patients and 20 healthy individuals using the KCL to assess frailty across seven structural domains. Hippocampal volumes were obtained from T1-weighted MRI images, and ROC analysis was performed to detect hippocampal atrophy. Results : Our results showed that patients with COPD had significantly greater atrophic left hippocampal volumes than healthy subjects ( p < 0.05). The univariate correlation coefficient between the left hippocampal volume and KCL (1-20), which pertains to instrumental and social activities of daily living, was the largest (ρ = -0.54, p < 0.0005) among the KCL subdomains. Additionally, both KCL (1-25) and KCL (1-20) demonstrated useful diagnostic potential (93% specificity and 90% sensitivity, respectively) for identifying individuals in the lowest 25% of the left hippocampal volume (AUC = 0.82). Conclusions : Our study suggests that frailty questionnaires focusing on daily vulnerability, such as the KCL, can effectively detect hippocampal atrophy in COPD patients.

The key to the practical application of organometal-halide crystals perovskite solar cells (PSCs) is to achieve thermal stability through robust encapsulation. This paper presents a method to significantly extend the thermal stability lifetime of perovskite solar cells to over 5000 h at 85 °C by demonstrating an optimal combination of encapsulation methods and perovskite composition for carbon-based multiporous-layered-electrode (MPLE)-PSCs. We fabricated four types of MPLE-PSCs using two encapsulation structures (over- and side-sealing with thermoplastic resin films) and two perovskite compositions ((5-AVA) x (methylammonium (MA)) 1-x PbI 3 and (formamidinium (FA)) 0.9 Cs 0.1 PbI 3 ), and analyzed the 85 °C thermal stability followed by the ISOS-D-2 protocol. Without encapsulation, FA 0.9 Cs 0.1 PbI 3 exhibited higher thermal stability than (5-AVA) x (MA) 1-x PbI 3 . However, encapsulation reversed the phenomenon (that of (5-AVA) x (MA) 1-x PbI 3 became stronger). The combination of the (5-AVA) x (MA) 1-x PbI 3 perovskite absorber and over-sealing encapsulation effectively suppressed the thermal degradation, resulting in a PCE value of 91.2% of the initial value after 5072 h. On the other hand, another combination (side-sealing on (5-AVA) x (MA) 1-x PbI 3 and over- and side-sealing on FA 0.9 Cs 0.1 PbI 3 ) resulted in decreased stability. The FACs-based perovskite was decomposed from these degradation mechanisms by the condensation reaction between FA and carbon. For side-sealing, the space between the cell and the encapsulant was estimated to contain approximately 1,260,000 times more H 2 O than in over-sealing, which catalyzed the degradation of the perovskite crystals. Our results demonstrate that MA-based PSCs, which are generally considered to be thermally sensitive, can significantly extend their thermal stability after proper encapsulation. Therefore, we emphasize that finding the appropriate combination of encapsulation technique and perovskite composition is quite important to achieve further device stability.

Purpose: This study aimed to investigate the intraoperative knee kinematics of cruciate-retaining total knee arthroplasty with a medial stabilising technique (MST-TKA) and compare the kinematics between mobile- and fixed-bearing MST-TKAs. We hypothesised that mobile-bearing MST-TKA would result in greater physiological kinematic motion than fixed-bearing MST-TKA., Methods: Twenty-one and 20 knees underwent mobile- and fixed-bearing MST-TKAs using a navigation system (Orthopilot® ver. 6.0; B. Braun Aesculap), respectively. In the preoperative and postoperative kinematic analysis, the knee was moved manually from 0° to 120°, and femoral anteroposterior translations of the medial femoral condyle (MFC) and lateral femoral condyle (LFC) were recorded every 0.1 s from 0° to 120°. Data were subsequently extracted from the software every 10° of flexion and compared between the two groups, and the correlation coefficients between preoperative and postoperative kinematics were calculated., Results: In the postoperative analysis, the MFC in the mobile-bearing group showed significant posterior translation at 100°, 110° and 120° compared to the fixed-bearing group ( p  < 0.01). Similarly, the LFC in the mobile-bearing group showed significant posterior translation at 100°, 110° and 120° compared to the fixed-bearing group ( p  < 0.05, p  < 0.01 and p  < 0.05, respectively). In the mobile-bearing group, the preoperative and postoperative anteroposterior translations of the MFC and LFC were correlated ( p  < 0.01), while in the fixed-bearing group, there was no correlation., Conclusion: The femoral rollback motion in the mobile-bearing MST-TKA correlated with the preoperative kinematics and was larger than that in the fixed-bearing group., Level of Evidence: Level II, therapeutic prospective cohort study., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Acid sphingomyelinase deficiency (ASMD) and Gaucher disease (GD) are lysosomal storage disorders associated with hepatosplenomegaly and thrombocytopenia. The incidences of ASMD and GD are known to be particularly high in the Ashkenazi Jewish population. Conversely, the number of reported patients with these diseases has been limited in Asian countries, including Japan. Here, we reviewed the allele frequencies of pathogenic variants causing ASMD and GD in the Japanese population and populations with various ancestry backgrounds using the Japanese Multi-Omics Reference Panel 54KJPN and the Genome Aggregation Database v4.0.0. The estimated carrier frequencies of ASMD- and GD-related variants were 1/180 and 1/154 in Japanese individuals, equivalent to disease occurrence frequencies of 1/128,191 and 1/94,791 individuals, respectively. These frequencies are much higher than previously expected. Our data also suggest that there are more patients with a milder form of ASMD and nonspecific clinical findings who have not yet been diagnosed., (© 2024. The Author(s).)

Purpose: The prognostic value of the lymphocyte-to-monocyte (LMR) ratio has been reported for various cancers, including colorectal cancer (CRC). The insertion of colonic stents is considered effective for patients with surgically indicated obstructive CRC, but their LMR can vary depending on factors such as inflammation associated with stent dilation and improvement of obstructive colitis. However, the usefulness of the LMR in patients with obstructive CRC and colonic stents and the optimal timing for its measurement remain unclear. We conducted this study to investigate the relationship between the pre-stent LMR and the mid-term prognosis of patients with obstructive CRC and stents as a bridge to surgery (BTS)., Methods: The subjects of this retrospective multicenter study were 175 patients with pathological stage 2 or 3 CRC. Patients were divided into a low pre-stent LMR group (n = 87) and a high pre-stent LMR group (n = 83)., Results: Only 3-year relapse-free survival differed significantly between the low and high pre-stent LMR groups (39.9% vs. 63.6%, respectively; p = 0.015). The pre-stent LMR represented a prognostic factor for relapse-free survival in multivariate analyses (hazard ratio 2.052, 95% confidence interval 1.242-3.389; p = 0.005), but not for overall survival., Conclusions: A low pre-stent LMR is a prognostic factor for postoperative recurrence in patients with obstructive CRC and a colonic stent as a BTS., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objective: We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan., Methods: Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID-19 pandemic (2020-2022)., Results: The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic (P = 0.020). Male and aging are high risk factors for death in older patients with IPD who had preceding influenza., Conclusion: Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults., Competing Interests: Declaration of competing interest The authors have no competing interests relevant to this article to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that plays a key role in the development and function of the liver, pancreas, and kidney. HNF1β plays a key role in early vertebrate development and the morphogenesis of these organs. In humans, heterozygous mutations in the HNF1B gene can result in organ dysplasia, making it the most common cause of developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. Pathogenic variants in the HNF1B gene are known to cause various diseases, including maturity-onset diabetes of the young and developmental renal diseases. This study presents the backbone resonance assignments of HNF1β POU S and POU HD domains, which are highly conserved domains required for the recognition of double-stranded DNA. Our data will be useful for NMR studies to verify the altered structures and functions of mutant HNF1B proteins that can induce developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. This study will provide the structural basis for future studies to elucidate the molecular mechanisms underlying how mutations in HNF1β cause diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The bleomycin-induced scleroderma model is a well-established and dependable method for creating a mouse model of SSc (systemic sclerosis). In the field of skin connective tissue diseases, increasing evidence from clinical and animal experiments suggests that TLRs (Toll-like receptors) play an important role in several diseases. This study aimed to determine the role of TLR7 (Toll-like receptor 7) and TLR9 (Toll-like receptor 9) in the mechanisms of immune abnormalities and fibrosis in SSc. This study used TLR7-KO mice (TLR7-knockout mice with a balb/c background) and TLR9-KO mice (TLR9-knockout mice with a balb/c background) as well as WT mice (wild-type balb/c mice). All three kinds of mice were induced by BLM (bleomycin) in a scleroderma model as the experimental group; meanwhile, WT mice treated with PBS (phosphate-buffered saline) were used as the control group. We analyzed the fibrotic phenotype and the immunological abnormality phenotype of TLR7-deficient and TLR9-deficient mice in the SSc disease model using flow cytometry, RT-PCR (reverse transcription-polymerase chain reaction), a histological examination, and IHC (immunohistochemical staining). In a mouse model of SSc disease, the deletion of TLR7 attenuated skin and lung fibrosis, while the deletion of TLR9 exacerbated skin and lung fibrosis. The deletion of TLR7 resulted in a relative decrease in the infiltration and expression of various pro-inflammatory and fibrotic cells and cytokines in the skin. On the other hand, the deletion of TLR9 resulted in a relative increase in the infiltration and expression of various pro-inflammatory and cytokine-inhibiting cells and cytokines in the skin. Under the influence of pDCs (plasmacytoid dendritic cells), the balances of Beff/Breg (IL-6 + CD19 + B cell/IL-10 + CD19 + B cell), Th17/Treg (IL-17A + CD4 + T cell/Foxp3 + CD25 + CD4 + T cell), M1/M2 (CD86 + macrophage/CD206 + macrophage), and Th1/Th2 (TNFα + CD3 + CD4 + T cell/IL-4 + CD3 + CD4 + T cell) were biased towards the suppression of inflammation and fibrosis as a result of the TLR7 deletion. Comparatively, the balance was biased towards promoting inflammation and fibrosis due to the TLR9 deletion. In the SSc model, TLR7 promoted inflammation and fibrosis progression, while TLR9 played a protective role. These results suggest that TLR7 and TLR9 play opposite roles in triggering SSc to produce immune system abnormalities and skin fibrosis.

Introduction: Tecovirimat's application in treating mpox remains under-researched, leaving gaps in clinical and virological understanding., Methods: The Tecopox study in Japan evaluated the efficacy and safety of tecovirimat in patients with smallpox or mpox, who were divided into oral tecovirimat and control groups. Patients with mpox enrolled between June 28, 2022, and April 30, 2023, were included. Demographic and clinical details along with blood, urine, pharyngeal swab, and skin lesion samples were gathered for viral analysis. A multivariable Tobit regression model was employed to identify factors influencing prolonged viral detection., Results: Nineteen patients were allocated to the tecovirimat group, and no patients were allocated to the control group. The median age was 38.5 years, and all patients were males. Ten patients (52.6%) were infected with human immunodeficiency virus (HIV). Sixteen patients (84.2%) had severe disease. Nine of the 15 patients (60.0%) (four patients withdrew before day 14) had negative PCR results for skin lesion specimens 14 days after inclusion. The mortality rates were 0% on days 14 and 30. No severe adverse events were reported. HIV status and the number of days from symptom onset to tecovirimat administration were associated with lower Ct values (p = 0.027 and p < 0.001, respectively). The median number of days when PCR testing did not detect the mpox virus in each patient was 19.5 days., Conclusion: Early tecovirimat administration might reduce viral shedding duration, thereby mitigating infection spread. Moreover, patients infected with HIV showed prolonged viral shedding, increasing the transmission risk compared to those without HIV., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Water is one of the most essential nutrients for life. The water turnover (WT), total body water (TBW), and total energy expenditure (TEE) can be measured using the doubly labeled water (DLW) method. WT and TBW are lower in older adults than in young adults, and the former are susceptible to dehydration, necessitating to identify predictors of the WT in older adults., Objectives: The current study aimed to examine the association between WT and physical activity, physical function, and body composition in Japanese adults aged ≥65 y and identify predictors for WT in this population., Methods: This study enrolled 133 older adults (women, n = 61; men, n = 72) aged 65-88 y. WT, TBW, TEE, fat-free mass (FFM), and percent body fat (%Fat) were determined using the DLW method. The fitness age score (FAS) was obtained from 5 physical fitness tests. Physical activity and the step count were assessed using a previously validated triaxial accelerometer. Multiple regression analyses were performed with WT as the dependent variable., Results: WT was positively associated with weight, physical activity level (PAL), moderate-vigorous physical activity, and TEE, and negatively associated with sedentary behavior. We examined potential predictors for WT using age, sex, height, weight, FFM, %Fat, TEE, PAL, and FAS in older Japanese adults., Conclusions: Our results confirmed that age, sex, weight, FFM, TEE, and PAL are the potential predictors of WT in older Japanese adults aged ≥65 y., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Pulmonary complications (PC) are a serious condition with a 20% mortality rate. However, few reports have examined risk factors for PC after colorectal surgery. This study investigated the frequency, characteristics, and risk factors for PC after colorectal cancer surgery., Methods: Between January 2016 and December 2022, we retrospectively reviewed 3979 consecutive patients who underwent colorectal cancer surgery in seven participating hospitals. Patients were divided into patients who experienced PC (PC group, n = 54) and patients who did not (non-PC group, n = 3925). Clinical and pathological features were compared between groups., Results: Fifty-four patients (1.5%) developed PC, of whom 2 patients (3.7%) died due to PC. Age was greater (80 years vs 71 years; p < 0.001), frequency of chronic obstructive pulmonary distress was greater (9.3% vs 3.2%; p = 0.029), performance status was poorer (p < 0.001), the proportion of underweight was higher (42.6% vs 13.4%, p < 0.001), frequency of open surgery was greater (24.1% vs 9.3%; p < 0.001), and blood loss was greater (40 mL vs 22 mL; p < 0.001) in the PC group. Multivariate analysis revealed male sex (odds ratio (OR) 2.165, 95% confidence interval (CI) 1.176-3.986; p = 0.013), greater age (OR 3.180, 95%CI 1.798-5.624; p < 0.001), underweight (OR 3.961, 95%CI 2.210-7.100; p < 0.001), and poorer ASA-PS (OR 3.828, 95%CI 2.144-6.834; p < 0.001) as independent predictors of PC., Conclusion: Our study revealed male sex, greater age, underweight, and poorer ASA-PS as factors associated with development of PC, and suggested that pre- and postoperative rehabilitation and pneumonia control measures should be implemented for patients at high risk of PC., (© 2024. The Author(s).)

Disturbances in sleep-wake and circadian rhythms may reportedly precede the onset of cognitive symptoms in the early stages of Alzheimer's disease (AD); however, the underlying mechanisms of these AD-induced sleep disturbances remain unelucidated. To specifically evaluate the involvement of amyloid beta (Aβ) oligomers in AD-induced sleep disturbances, we examined circadian and sleep phenotypes using an Aβ-GFP transgenic (Aβ-GFP Tg) mouse characterized by intracellular accumulation of Aβ oligomers. The circadian rhythm and free-running period of wheel running activity were identical between Aβ-GFP Tg and littermate wild-type mice. The durations of rapid eye movement (REM) sleep were elongated in Aβ-GFP Tg mice; however, the durations of non-REM sleep and wakefulness were unaffected. The Aβ-GFP Tg mice exhibited shifts in the electroencephalogram (EEG) power spectra toward higher frequencies in the inactive light phase. These findings suggest that the intracellular accumulation of Aβ oligomers might be associated with sleep quality; however, its impact on circadian systems is limited.

Anti-human upstream-binding factor (anti-hUBF) antibodies have been reported predominantly in patients with connective tissue diseases (CTDs); these have also been reported in patients without CTDs such as hepatocellular carcinoma. Because of the low frequency of expression and few case reports, there is no consensus on the clinical significance of these antibodies. Thus, we aimed to examine the clinical features of patients with anti-hUBF antibodies and analyzed 1042 patients with clinically suspected CTDs. The presence of anti-hUBF antibodies was screened using immunoprecipitation assays. Of the 1042 patients, 19 (1.82%) tested positive for anti-hUBF antibodies; among them, 10 (56%) were diagnosed with undifferentiated CTD (UCTD), six with systemic sclerosis (SSc) and three with other diseases. Five of the 10 patients with UCTD were referred to our hospital with suspected SSc. None of the five patients fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria, but three scored seven points, a relatively high score. Six anti-hUBF-positive patients with SSc had a significantly lower modified Rodnan skin score (mRSS) than that of anti-hUBF-negative patients with SSc (2 [0-2] vs 7 [0-49], p < 0.01). Compared with anti-topoisomerase I-positive patients, anti-hUBF-positive patients had a significantly lower mRSS (2 [0-2] vs 13 [0-42], p < 0.01) and lower incidence of scleroderma renal crisis (0 of 6 vs 8 of 184, p < 0.01). Compared with anti-centromere-positive patients, anti-hUBF-positive patients had a higher incidence of interstitial lung disease (ILD), but the difference was not statistically significant (4 of 6 vs 19 of 239). In conclusion, anti-hUBF antibodies were predominantly detected in patients with CTDs and UCTD. In patients with CTDs, SSc exhibited a high ratio, displaying a lower mRSS and higher incidence of ILD. In patients with UCTD, careful follow-up is recommended as they may develop CTDs in the future., (© 2024 Japanese Dermatological Association.)