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Background: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has recently been reported as a distinct type of TBI in infancy. However, the pathological and prognostic factors of TBIRD remain unknown. We aimed to compare patients with and without TBIRD and evaluate the pathomechanism of TBIRD using magnetic resonance spectroscopy (MRS)., Methods: Ten Japanese patients with TBI were admitted to our hospital and underwent MRS between September 2015 and September 2022 (age range, 3-15 months; median age, 8.5 months). TBIRD was diagnosed in six patients. MRS data were compared among patients with TBIRD, patients without TBIRD, and controls. Neurological prognosis was classified into grades 1 (normal) to 3 (severe)., Results: In patients with TBIRD, MRS revealed an increase in the glutamine (Gln) level on days 3-29, which subsequently became close to normal. The degree of Gln elevation in the non-TBIRD group was smaller (117-158 % of controls) than that in the TBIRD group (210-337 %) within 14 days. MRS in the TBIRD group showed decreased N-acetyl aspartate (NAA) concentrations. The degree of NAA decrease was more prominent in grade 3 than in grades 1 and 2. NAA levels in the non-TBIRD group were almost normal., Conclusions: Patients with TBI and markedly elevated Gln levels on MRS may develop TBIRD. Neuro-excitotoxicity is a possible pathological mechanism of TBIRD. Decreased NAA levels may be useful for predicting the prognosis of patients with TBIRD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Three isoforms of secretoglobin (SCGB) 3A2, namely type A, B, and C, are endogenously produced through alternative splicing. SCGB3A2 type A, the correctly spliced major type, begins to be expressed from embryonic day 11.5 in mice and shows various physiological activities such as promoting lung maturation and bronchial branching, anti-inflammatory effects, and ameliorating induced pulmonary fibrosis. To investigate the potential of SCGB3A2 peptides as a therapeutic to treat respiratory diseases, in this study, serially overlapping nine peptides were synthesized to cover the entire type C isoform, and five and one peptides covering the C-terminal region of type A and B, respectively. To evaluate their biological activities, each peptide was subjected to cell proliferation and apoptosis analyses in vitro using mouse lung fibroblast-derived MLg cells, bronchial branching rate using ex vivo mouse fetal lung organ cultures, and in vivo allergic airway inflammation mouse model. Among type A and C peptides, those corresponding to the C-terminal region of the SCGB3A2 sequence exhibited its unique biological activities of promoting cell proliferation and bronchial branching, and/or inhibiting apoptosis. The type B peptide did not show any proliferative effect while inhibited apoptosis. In a mouse model of allergic airway inflammation, lung inflammation was improved by the administration of most of the C-terminal region-derived type A and type C peptides. The results suggest that the bioactivity resides towards the C-terminal region of SCGB3A2 sequence, and the peptides covering this region could be used as a therapeutic in treating lung inflammation., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024. Published by Elsevier Inc.)

A pleural effusion is a common pulmonary manifestation of systemic lupus erythematosus (SLE), and differential diagnosis is needed to perform targeted treatments. An SLE patient with refractory chylothorax is presented. Chylothorax rarely occurs in SLE patients and occasionally follows a refractory clinical course despite intensive treatment with immunosuppressive therapies, resulting in a poor prognosis with malnutrition caused by frequent thoracenteses. In such cases, pleuro-peritoneal and peritoneal-venous shunts along with cell-free and concentrated ascites re-infusion therapy might be effective to improve the dyspnea while maintaining nutrition., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

The survival outcomes of patients with chronic myeloid leukemia (CML) have significantly improved due to the introduction of adenosine triphosphate (ATP) -competitive ABL1 tyrosine kinase inhibitors (TKIs). However, several patients with CML eventually develop treatment resistance or intolerance during the course of ATP-competitive ABL1 TKI treatment. ABL1 TKIs inhibit other tyrosine kinases via their off-target effects. This mechanism leads to the development of adverse events, which may result in treatment discontinuation. Asciminib is a first-in-class STAMP (specifically targeting the ABL myristoyl pocket) inhibitor used in patients with chronic-phase CML who exhibit resistance or intolerance to two prior TKI therapies. Asciminib was found to have excellent efficacy and safety therapeutic profiles. The lack of comprehensive reviews about asciminib, thus, the current study aimed to evaluate the clinical and preclinical evidence of the efficacy and safety of asciminib., Competing Interests: Disclosure HU declares honoraria from Novartis. SK received honoraria from Pfizer, Otsuka Pharmaceuticals, Novartis and Bristol-Myers-Squibb, and research funding from Pfizer, Bristol-Myers-Squibb and Ohara Pharmaceuticals., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The effect of radical nephroureterectomy (RNUx) on postoperative renal function in patients diagnosed with upper tract urothelial carcinoma (UTUC) has not been thoroughly explored., Methods: We conducted a retrospective analysis including 785 patients who underwent RNUx for UTUC. We assessed the preoperative and postoperative estimated glomerular filtration rates (eGFRs) and factors related to the decline in eGFR. Additionally, we examined the effect of comorbidities (diabetes or hypertension) on the postoperative eGFR at 1 year. Cox proportional hazard models were employed to investigate the clinical effect of RNUx on oncological outcomes, including non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS)., Results: The median preoperative and postoperative eGFR levels were 54.7 and 40.6 ml/min/1.73 m 2 respectively. The proportions of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m 2 were 35.9% and 5.1%, respectively. The median decline in the eGFR after surgery was 26.8%. Patients with preoperative eGFR <60 ml/min/1.73 m 2 demonstrated significantly lower odds of a postoperative decline in eGFR of 25% or more. The effect of comorbidities on postoperative eGFR at 1 year was significant (P = 0.048). The 3-year NUTRFS, CSS, and OS rates were 72.9%, 85.2%, and 81.5%, respectively. Preoperative chronic kidney disease was an independent factor associated with inferior NUTRFS, CSS, and OS., Conclusion: Different degrees of impairment of renal function occur among UTUC patients. Only 5.1% of patients retain a postoperative eGFR ≥60 ml/min/1.73 m 2 . Preoperative renal impairment was linked to reduced odds of postoperative eGFR decrease and associated with survival. In addition, the presence of comorbidities had a significant effect on the decline in eGFR. These findings emphasize the importance of developing evidence-based perioperative treatment strategies for UTUC patients with impaired renal function., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study aimed to quantify the readability and quality of online patient resources on knee osteoarthritis and lumbar spinal stenosis in Japan., Methods: Three search engines (Google, Yahoo, and Bing) were searched for the terms knee osteoarthritis and lumbar spinal stenosis. The first 30 websites of each search were screened. Duplicate websites and those unrelated to the searched diseases were excluded. The remaining 125 websites (62 on knee osteoarthritis, 63 on lumbar spinal stenosis) were analyzed. The text readability was assessed using two web-based programs (Obi-3 and Readability Research Lab) and lexical density. Website quality was evaluated using the DISCERN score, Clear Communication Index, and Journal of American Medical Association benchmark criteria., Results: Readability scores were high, indicating that the texts were difficult to understand. Only 24 (19%) and six (5%) websites were classified as average difficulty readability according to Obi-3 and Readability Research Lab, respectively. The overall quality of information was low, with only four (3%) being rated as having sufficient quality based on the Clear Communication Index and Journal of American Medical Association benchmark criteria. None of the websites satisfied the DISCERN quality criteria., Conclusions: Patient information on Japanese websites regarding knee osteoarthritis and lumbar spinal stenosis were difficult to understand. Moreover, the quality of the websites was insufficient. Orthopaedic surgeons should contribute to the creation of high-quality easy-to-read websites to facilitate patient-physician communication., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: We aimed to evaluate the intra- and interrater measurement reliability of the lateral ankle ligament attachment locations using three-dimensional magnetic resonance imaging., Methods: We analysed 54 participants with a mean age of 43 years who underwent three-dimensional ankle magnetic resonance imaging and had normal lateral ligaments. Bony landmarks of the distal fibula, talus, and calcaneus were identified in the reconstructed images. The centers of the anterior talofibular ligament and calcaneofibular ligament attachments were also identified. The distances between the landmarks and attachments were measured. Two raters performed the measurements twice, and intra- and interrater intraclass correlation coefficients were calculated., Results: The intrarater intraclass correlation coefficient values were between 0.71 and 0.96 for the anterior talofibular ligament attachment measurements and between 0.77 and 0.95 for the calcaneofibular ligament attachments. The interrater intraclass correlation coefficient was higher than 0.7, except for the distance between the anterior talofibular ligament superior bundle and fibular obscure tubercle. The fibular attachment of a single-bundle anterior talofibular ligament was located 13.3 mm from the inferior tip and 43% along the anterior edge of the distal fibula. The superior and inferior bundles of the double-bundle ligament were located at 43% and 23%, respectively. The calcaneofibular ligament fibular attachment was 5.5 mm from the inferior tip, at 16% along the anterior edge of the distal fibula., Conclusion: The measurements of anterior talofibular ligament and calcaneofibular ligament attachment locations identified on three-dimensional magnetic resonance imaging were sufficiently reliable. This measurement method provides in vivo anatomical data on the lateral ankle ligament anatomy., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: This study aimed to report the outcome of deep infections of the foot and ankle, which are among the most challenging orthopedic conditions to treat, after continuous local antibiotic perfusion., Methods: Eleven patients with deep foot and ankle infections were treated with continuous local antibiotic perfusion between January 2019 and March 2024. After surgical debridement, we performed continuous perfusion of high concentrations of gentamicin (60 mg/50 ml) directly into the infected bone and soft tissue for two weeks using bone marrow needles and double-lumen tubes. Patient characteristics, infection relapse, and adverse events were investigated., Results: The mean age of the patients was 53 years (range 12-79 years), with six males and five females. The infections were controlled without additional surgeries in ten patients with a mean follow-up of 40 months (12-62 months). Two patients developed a fungal infection, of which one required an additional debridement surgery, and the other was treated with oral antifungal medication. No adverse events occurred due to high-concentration gentamicin., Conclusions: Short-term infection control was achieved using continuous local antibiotic perfusion; thus, it can be a treatment option for deep infections of the foot and ankle., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: In endovascular aortic repair (EVAR), preemptive embolization of sac branch vessels is effective in preventing postoperative type II endoleak (T2EL). However, this technique has not been widely adopted especially for lumbar arteries (LAs) because of technical difficulties and time constraints. This study aimed to investigate the efficacy of nonselective sac coil embolization, which is a simpler surgical method, in postoperative sac shrinkage for patients at a high risk of T2EL from LAs., Methods: We retrospectively assessed 76 patients who underwent elective EVAR for abdominal aortic aneurysm with 4 or more patent LAs or at least 1 patent LA of ≥2 mm at our hospital between January 2014 and December 2022. The patients who underwent sac coil embolization were included in Group Ⅰ (n = 20), and the others were divided into 2 groups: those with an inferior mesenteric artery that was originally occluded or embolized by coils or stent graft bodies (Group Ⅱ, n = 21), and those without that (Group Ⅲ, n = 35). In Group Ⅰ, 0.035-inch coils were inserted into the sac after complete stent graft deployment. The cumulative incidence of sac shrinkage (≥5 mm) was compared between the groups. Further, univariable and multivariable Cox regression analyses were used to determine the predictors of sac shrinkage., Results: Sac shrinkage (≥5 mm) was observed more frequently in Group Ⅰ (50%) than in Group Ⅱ (19%) and Group Ⅲ (17%) (P = 0.052 and 0.043, respectively). The cumulative incidence of sac shrinkage was significantly higher in Group Ⅰ than in Group Ⅱ (log-rank P = 0.039) and Group Ⅲ (log-rank P = 0.024). Multivariable Cox regression analyses revealed that sac embolization was a significant predictor of sac shrinkage (hazard ratio, 4.23; 95% confidence interval, 1.66-10.8; P = 0.003)., Conclusions: Nonselective sac coil embolization in EVAR is potentially effective for sac shrinkage in the early postoperative phase in patients at high risk of T2EL from LAs. This simple procedure may improve prognosis after EVAR., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The CheckMate274 trial has reported enhanced disease-free survival rates in patients with stage pT3-4/ypT2-4 or pN+ urothelial carcinoma (UC) undergoing adjuvant nivolumab therapy. This study compares prognostic differences between urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC)., Methods: We retrospectively analyzed data from 719 patients with UC who underwent radical surgery, stratifying to patients at stage pT3-4 and/or pN+ without neoadjuvant chemotherapy (NAC) or at ypT2-4 and/or ypN+ with NAC (potential candidates for adjuvant immunotherapy), and to those who were not candidates for adjuvant immunotherapy. We used Kaplan-Meier curves to assess oncological outcomes, particularly nonurothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Risk factors were identified by Cox regression analysis., Results: Kaplan-Meier curves showed significantly lower NUTRFS, CSS, and OS for potential adjuvant immunotherapy candidates than for noncandidates in each UCB and UTUC group. NUTRFS, CSS, and OS did not differ significantly between adjuvant immunotherapy candidates with UBC or UTUC. Trends were similar among patients ineligible for adjuvant immunotherapy. Pathological T stage (pT3-4 or ypT2-4), pathological N stage, and lymphovascular invasion (LVI) were independent predictors of oncological outcomes on multivariate analysis., Conclusion: The criteria for adjuvant immunotherapy candidates from the CheckMate 274 trial can also effectively stratify UC patients after radical surgery. Substantial clinical significance is attached to LVI status as well as to pathological T and N status, suggesting that LVI status should be considered when selecting suitable candidates for adjuvant immunotherapy., Competing Interests: Disclosure The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The critical role of radiographic assessment at the time of castration-resistant prostate cancer (CRPC) diagnosis is underscored by this study. We performed a retrospective analysis of radiographic changes in metastasis from the time of diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) to CRPC diagnosis. We also explored its impact on prognosis post-CRPC., Materials and Methods: We retrospectively analyzed 98 men who underwent radiographic examinations (bone scans and computed tomography [CT]) at the time of CRPC diagnosis. When radiographic studies demonstrated progression at CRPC diagnosis, patients were assigned to the radiographic progressive disease (rPD) group. The remaining patients were placed in the "non-rPD" group. The overall survival (OS) post-CRPC was compared between the 2 groups., Results: The median OS post-CRPC was significantly shorter in the rPD group (n = 50) compared to the non-rPD group (n = 48) (32 months vs. not reached, P = .0124). Multivariate analysis showed that radiographic progression and shorter time to CRPC were associated with a shorter OS post-CRPC (hazard ratio [HR] = 3.14; 95% confidence interval [CI], 1.21-8.12, P = .019)., Conclusion: Radiographic progression at the point of CRPC diagnosis independently predicts a shorter OS post-CRPC in patients with mHSPC. Therefore, assessing radiographic changes at the time of CRPC diagnosis could be instrumental in managing CRPC in patients with mHSPC., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Lower limb flexibility (LLF) is an essential motor function. However, assessing LLF during adolescence is difficult because of the influence of marked physical changes. We, therefore, assessed LLF and investigated the relationship between LLF and sex and age in healthy children and adolescents., Methods: We conducted a five-year cross-sectional study with students aged 8-14 years at a single school in Japan. We evaluated the heel-buttock distance (HBD), straight leg raising angle (SLRA), and dorsiflexion angle of the ankle joint (DFA) at the beginning of each year. We conducted a comparative analysis on the performance of the HBD, SLRA, and DFA techniques, stratified by both sex and age. The statistical significance of observed differences was assessed through the application of Mann-Whitney U and Kruskal-Wallis tests. Furthermore, we analyzed the effects of sex, age, height, and weight on LLF using a multivariable linear regression model., Results: Of the 4221 initial study participants, 3370 were analyzed. Mean HBD, SLRA, and DFA values were 1.6 cm, 77.0°, and 15.7°, respectively. Girls showed significantly higher HBD and lower SLRA and DFA values than boys and 14-year-olds (p < 0.01). Median HBD value for girls was 0 cm, whereas for boys, it exceeded 0 cm after age 13. The median SLRA value for girls was 80-85°, while for boys, it was 70-75°. The median DFA value for girls was 15-19°, and for boys, it was 12-15°. A multivariable linear regression model indicated that boys had significantly greater tightness than girls (p < 0.01)., Conclusions: The reference values of HBD, SLRA, and DFA differed according to age and sex. Furthermore, we showed that sex differences were significantly associated with LLF. Data in this study provide the reference value for assessing LLF in children and adolescents., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Long-term survival outcomes of patients with chronic myeloid leukemia in the chronic phase are now similar to those of the general population, following the introduction of ABL1 tyrosine kinase inhibitors (TKIs). Approximately 40% to 80% of patients with chronic myeloid leukemia successfully achieved treatment-free remission after the first attempt of TKI discontinuation (TFR1), after achieving a durable deep molecular response. However, the possibility of achieving treatment-free remission after a second attempt of TKI discontinuation (TFR2) remains unclear. Therefore, we reviewed current TFR2 studies to clarify the feasibility of achieving TFR2. We identified 5 TFR2 clinical trials and 2 real-world reports. TFR2 attempt may be feasible after retreatment with imatinib, nilotinib, or dasatinib. Patients who have achieved MR 4.0 or deeper durable molecular remission are eligible to enter the TFR2 phase. Imatinib is well tolerated and can be administered for consolidative treatment before the TFR2 attempt, whereas drug-related adverse effects of nilotinib or dasatinib affect their tolerability and might lead to discontinuation. Late onset relapse (> 1 year or > 2 year) was often reported, thus careful monitoring is needed., Competing Interests: Disclosure SK received honoraria from Bristol-Myers-Squibb, Novartis, Pfizer, and Otsuka Pharmaceuticals and research funding from Bristol-Myers-Squibb, Pfizer, and Ohara Pharmaceuticals. The other authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nanocatalysts tend to aggregate and are difficult to recycle, limiting their practical applications. In this study, an environmentally friendly method was developed to produce cellulose beads for use as supporting materials for Cu-based nanocatalysts. Cellulose beads were synthesized from a water-in-oil emulsion using cellulose dissolved in an LiBr solution as the water phase and vegetable oil as the oil phase. Upon cooling, the gelation of the cellulose solution produced spherical cellulose beads, which were then oxidized to introduce surface carboxyl groups. These beads (diameter: 95-105 μm; specific surface area: 165-225 m 2  g -1 ) have a three-dimensional network of nanofibers (width: 20-30 nm). Furthermore, the Cu 2 O nanoparticles were loaded onto oxidized cellulose beads before testing their catalytic activity in the reduction of 4-nitrophenol using NaBH 4 . The apparent reaction rate constant increased with increasing loading of Cu 2 O nanoparticles and the conversion efficiency was >90 %. The turnover frequency was 376.2 h -1 for the oxidized cellulose beads with the lowest Cu 2 O loading, indicating a higher catalytic activity compared to those of other Cu-based nanoparticle-loaded materials. In addition to their high catalytic activity, the cellulose beads are reusable and exhibit excellent stability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT)., Methods: We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P., Results: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003)., Conclusion: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P., Competing Interests: Disclosure The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Ozone is one of the triggers of asthma, but its impact on the pathophysiology of asthma, such as via airway inflammation and airway hyperresponsiveness (AHR), is not fully understood. Thymic stromal lymphopoietin (TSLP) is increasingly seen as a crucial molecule associated with asthma severity, such as corticosteroid resistance., Methods: Female BALB/c mice sensitized and challenged with house dust mite (HDM) were exposed to ozone at 2 ppm for 3 h. Airway inflammation was assessed by the presence of inflammatory cells in bronchoalveolar lavage fluid and concentrations of cytokines including TSLP in lung. Anti-TSLP antibody was administered to mice to block the signal. Survival and adhesion of bone marrow-derived eosinophils in response to granulocyte colony-stimulating factor (G-CSF) were evaluated., Results: Ozone exposure increased eosinophilic airway inflammation and AHR in mice sensitized and challenged with HDM. In addition, TSLP, but not IL-33 and IL-25, was increased in lung by ozone exposure. To confirm whether TSLP signaling is associated with airway responses to ozone, an anti-TSLP antibody was administered, and it significantly attenuated eosinophilic airway inflammation, but not AHR. Interestingly, G-CSF, but not type 2 cytokines such as IL-4, IL-5, and IL-13, was regulated by TSLP signaling associated with eosinophilic airway inflammation, and G-CSF prolonged survival and activated eosinophil adhesion., Conclusions: The present data show that TSLP contributes to ozone-induced exacerbations of eosinophilic airway inflammation and provide greater understanding of ozone-induced severity mechanisms in the pathophysiology of asthma related to TSLP and G-CSF., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: Most long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established., Methods: We retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months. There were three patients enrolled in our study (3, 4 and 16 years of age) who had severe impairment of gross motor function without head control or the ability to roll over. All three needed mechanical ventilation with tracheostomy and tube feeding. Motor function was assessed using the Children s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) and the caregivers' evaluations. Concurrently, we examined nerve conduction longitudinally and compared compound motor action potential (CMAP) amplitudes., Results: All patients continued nusinersen administration without significant adverse events for more than three years. While CHOP-INTEND scores did not remarkably increase, according to the caregivers, all three patients had improved finger or facial muscle movements that enabled them to make their intentions understood. Some CMAPs before treatment were not identified but became traces after nusinersen administration., Conclusions: The improvement in motor function that leads to smoother communication could be a basis for continuing nusinersen treatment. Currently available motor function scorings are not efficient for assessing therapeutic interventions in SMA patients with medical care complexity. Longitudinal nerve conduction studies could be an objective indicator., 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 © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has been reported as a type of TBI. However, it remains uncertain which pediatric patients with TBI develop TBIRD., Methods: Patients with TBI who were admitted to our hospital and underwent magnetic resonance imaging (MRI) between December 2006 and October 2022 were included in this study. A diagnosis of TBIRD was made in patients with or suspected TBI, with initial symptoms being convulsions or disturbance of consciousness and late-onset subcortical reduced diffusion, the so-called bright tree appearance. Clinical features, neuroimaging (computed tomography (CT) and MRI) findings, laboratory data, and Tada score were retrospectively compared between TBIRD and non-TBIRD patients. Neurological prognosis was assessed using the Pediatric Cerebral Performance Category scale., Results: Of 21 patients who met the inclusion criteria, a diagnosis of TBIRD was made in 7 patients (median age: 8 months). The factors contributing to TBIRD development were seizures lasting over 30 min as the initial symptom (5/7 in TBIRD vs. 0/14 in non-TBIRD), tracheal intubation during initial treatment (5/7 vs. 0/14), and brain parenchymal lesions on CT (3/7 vs. 0/14), suggesting that severe TBI may progress to TBIRD. The Tada score was more positive in patients with TBIRD (6/7) than in those without (0/14)., Conclusions: It is important to monitor infant patients with severe TBI for the development of TBIRD. The Tada score can be a useful tool for TBIRD prediction., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to clarify the variability in the measurements of stress sonography of the ankle and determine the effects of examiner experience on the measurements., Methods: Twenty examiners (10 experienced and 10 beginners) were included in the study. Each examiner performed stress ultrasonography on a patient with a chronic anterior talofibular ligament injury and a patient with an intact ligament using the reverse anterior drawer method. Changes in ligament length before versus after stress were determined. The same 20 examiners performed ultrasonography on two other patients with an injured or intact ATFL using the anterior drawer method. The length change values and variance were compared between the groups using t-tests and F-tests., Results: Using the reverse anterior drawer method, the change in the anterior talofibular ligament length was 3.3 mm (range, 2.2-4.8 mm) in the experienced group and 2.7 mm (0.0-4.1 mm) in the beginner group for the ligament injured patient. The length changes for the patient with intact anterior talofibular ligament were 0.5 mm (0.1-0.9 mm) and 0.4 mm (-0.1-1.5 mm) in the experienced and beginner groups, respectively. There were no significant intergroup differences in measurement amount (P = 0.37) or variance (P = 0.72). Similarly, using the anterior drawer method, no significant differences between the groups were found in measurement amount or variance., Conclusion: The quantitative evaluation of stress sonography of the ankle was variable regardless of examiner experience or stress method, particularly in patients with an anterior talofibular ligament injury. The amount of variability appeared to be unacceptably large for clinical application. Our study results highlight the need for technical standardization., Competing Interests: Declaration of competing interest The ultrasonography machine used in this study was provided by the Sonography for MSK Activating Project., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Transcutaneous auricular vagus nerve stimulation (taVNS) was performed in two patients suffering structural focal epilepsy with preserved intellectual ability to show the feasibility of taVNS for specific patient groups., Case Presentations: Patient 1 was a 24-year-old woman with frontal lobe epilepsy who had weekly hyperkinetic seizures despite multiple anti-seizure medications. Patient 2 was a 27-year-old woman with parietal lobe epilepsy and focal cortical dysplasia in the vicinity of the lipoma in the corpus callosum. She experienced weekly focal-impaired awareness seizures even with anti-seizure medication. taVNS was applied to the left earlobe of both patients at 1.5 mA, 25 Hz, 250 μs pulse width, and 30 s stimulation with 30 s rest for 4 h per day. Over an 8-week baseline and 20 weeks of stimulation, the rate of reduction in seizure frequency was evaluated, along with quality-of-life using the Short-Form 36-Item Health survey., Results: At baseline, we measured up to 11 and 12 focal seizures per week in Patient 1 and 2, respectively, with both patients achieving seizure freedom after 4 and 20 weeks taVNS, respectively. Patient 1 and 2 were observed for 18 and 14 months, respectively, including the clinical trial and follow-up observation period. Quality-of-life ratings increased in both patients, and no significant adverse events occurred during the study period. During the maintenance period after 20 weeks, seizures remained absent in Patient 1, and seizures remained reduced in Patient 2., Conclusion: Our results demonstrate that taVNS may be a promising tool for structural focal epilepsy with preserved cognitive function. A multicenter double-blind clinical trial is needed to confirm the role of taVNS as an anti-seizure tool., 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 © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

We demonstrated that a unique polysaccharide with extremely high molecular weight can be easily obtained via a low-cost, mild reaction in a water medium from sucrose, a photosynthetic product. α-1,3/1,6-Glucosyltransferase L (GtfL) from Streptococcus salivarius produced water-insoluble α-d-glucan from sucrose at 37 °C. Gel permeation chromatography revealed the molecular weight was extremely high; the weight-average molecular weight values were more than 1,000,000 irrespective of the substrate concentration. The Smith degradation of neat glucan and NMR spectroscopic analyses of the acetyl derivative revealed a structure similar to that of a comb-type graft copolymer, α-d-(1 → 3)-graft-(1 → 6)-glucan. The anhydroglucose units (AGUs) in the main-chain backbone are linked by (1 → 3)-glycosidic bonds, whereas a side chain consisting of four AGUs via (1 → 6)-glycosidic bonds alternately extends from C6 of the main chain., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: In quantitative ankle stress sonography, different examiners use different techniques, which may cause measurement variability. This study aimed to clarify whether standardizing stress sonography techniques reduces variability in the quantitative measurement of anterior talofibular ligament length change., Methods: Fourteen examiners with a mean ultrasound experience of 8.7 years participated in this study. Each examiner performed stress ultrasonography of the ankle using their preferred method on one patient with an intact anterior talofibular ligament (Patient 1) and on two patients with chronic ankle instability (Patient 2 and 3). Changes in the ligament length between the resting and stressed positions were determined. A consensus meeting was then conducted to standardize the sonographic technique, which was used by the examiners during a repeat stress sonography on the same patients. The variance and measured values were compared between the preferred and standardized techniques using F-tests and paired t-tests, respectively., Results: At a consensus meeting, a sonographic technique in which the examiner pushed the lower leg posteriorly against the fixed foot was adopted as the standardized technique. In Patient 1, the change in the anterior talofibular ligament length was 0.4 (range, -2.3-1.3) mm and 0.6 (-0.6-1.7) mm using the preferred and standardized techniques, respectively, with no significant difference in the variance (P = 0.51) or the measured value (P = 0.52). The length changes in Patient 2 were 2.0 (0.3-4.4) mm and 1.7 (-0.9-3.8) mm using the preferred and standardized techniques, respectively. In Patient 3, the length changes were 1.4 (-2.7-7.1) mm and 0.7 (-2.0-2.3) mm. There were no significant differences between the techniques in either patient group., Conclusion: Variability in the quantitative measurement of ankle stress sonography was not reduced despite the standardization of the technique among examiners. Hence, comparing the measured values between different examiners should be avoided., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background: Intrawound vancomycin powder is effective in preventing surgical site infection after spine surgery. In a previous study, vancomycin-induced cytotoxicity in osteoblasts was investigated in vitro, and vitamin D3 was verified to be a candidate drug aiding recovery from vancomycin-induced cytotoxicity. The treatment practices involving osteogenesis-promoting drugs vary widely. Teriparatide, an anabolic agent, highly promotes bone formation by inducing osteoblast activation, increasing bone formation and mineral density, and preventing vertebral fractures. Hence, teriparatide may be administered in combination with vancomycin., Methods: MC3T3-E1 cells were cultured in minimum essential medium supplemented with 10% fetal bovine serum at 37 °C in a humidified incubator containing 5% CO 2 . The experimental concentrations of vancomycin (2500, 5000, and 7500 μg/mL) were determined based on previous reports and our preliminary experiments. Teriparatide (100 ng/mL) was administered concomitantly to prevent cytotoxicity in osteoblasts, using pulsed vancomycin for 24 h (measured at 1, 3, and 7 days). Cell numbers and morphological changes in cells treated with vancomycin or vancomycin plus 100 ng/mL teriparatide were measured. Osteoblast differentiation was assessed using alkaline phosphatase staining, alkaline phosphatase activity, and alizarin red S staining., Results: Teriparatide showed a recovery effect when vancomycin (7500 μg/mL) was administered only for 24 h. Microscopic examination revealed that teriparatide had a protective effect on osteoblasts exposed to 7500 μg/mL vancomycin. Addition of teriparatide led to the recovery of alkaline phosphatase staining and alizarin red staining., Conclusion: Vancomycin-induced cytotoxicity in osteoblasts could be inhibited by administering teriparatide concomitantly with vancomycin., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

This study sought to develop a specific and sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for pharmacokinetic studies of dasatinib, a tyrosine kinase inhibitor. Anti-dasatinib antibodies were obtained from mice or rabbits by using two partial structures of dasatinib as haptens: 2-amino-N-(2-chloro-6-methylphenyl)-thiazole-5-carboxamide and 2-{4-(2-hydroxyethyl)-1-piperazinyl}-isonicotinic acid. The best combination of two antibodies for sandwich ELISA of dasatinib was determined using four anti-dasatinib antibodies derived from mice and rabbits. Using two dasatinib-specific rabbit antibodies, we successfully developed an ultra-specific and highly sensitive sandwich ELISA that is hardly affected by the main metabolite of dasatinib. The sandwich ELISA showed a linear detection range from 320 pg/mL to 1000 ng/mL. Serum dasatinib concentrations lower than 320 pg/mL were reproducibly measurable using the sandwich ELISA. The ELISA was specific to dasatinib and there were no cross-reactivities with the major metabolites 4'-hydroxy dasatinib and dasatinib carboxylic acid. The developed sandwich ELISA will be a valuable tool for pharmacokinetic studies of dasatinib. Furthermore, this study revealed that rabbit antibodies can sandwich drug molecules of a smaller size than mouse antibodies in sandwich ELISA., 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 © 2023 Elsevier Inc. All rights reserved.)

Background: Delayed-onset paraplegia is a disastrous complication after thoracoabdominal aortic open surgery and thoracic endovascular aortic repair. Studies have revealed that transient spinal cord ischemia caused by temporary occlusion of the aorta induces delayed motor neuron death owing to apoptosis and necroptosis. Recently, necrostatin-1 (Nec-1), a necroptosis inhibitor, has been reported to reduce cerebral and myocardial infarction in rats or pigs. In this study, we investigated the efficacy of Nec-1 in delayed paraplegia after transient spinal cord ischemia in rabbits and assessed the expression of necroptosis- and apoptosis-related proteins in motor neurons., Methods: This study used rabbit transient spinal cord ischemia models using a balloon catheter. They were divided into a vehicle-treated group (n = 24), Nec-1-treated group (n = 24), and sham-controls (n = 6). In the Nec-1-treated group, 1 mg/kg of Nec-1 was intravascularly administered immediately before ischemia induction. Neurological function was assessed using the modified Tarlov score, and the spinal cord was removed 8 hr and 1, 2, and 7 days after reperfusion. Morphological changes were examined using hematoxylin and eosin staining. The expression levels of necroptosis-related proteins (receptor-interacting protein kinase [RIP] 1 and 3) and apoptosis-related proteins (Bax and caspase-8) were assessed using western blotting and histochemical analysis. We also performed double-fluorescence immunohistochemical studies of RIP1, RIP3, Bax, and caspase-8., Results: Neurological function significantly improved in the Nec-1-treated group compared with that in the vehicle-treated group 7 days after reperfusion (median 3 and 0, P = 0.025). Motor neurons observed 7 days after reperfusion were significantly decreased in both groups compared with the sham group (vehicle-treated, P < 0.001; Nec-1-treated, P < 0.001). However, significantly more motor neurons survived in the Nec-1-treated group than in the vehicle-treated group (P < 0.001). Western blot analysis revealed RIP1, RIP3, Bax, and caspase-8 upregulation 8 hr after reperfusion in the vehicle-treated group (RIP1, P = 0.001; RIP3, P = 0.045; Bax, P = 0.042; caspase-8, P = 0.047). In the Nec-1-treated group, the upregulation of RIP1 and RIP3 was not observed at any time point, whereas that of Bax and caspase-8 was observed 8 hr after reperfusion (Bax, P = 0.029; caspase-8, P = 0.021). Immunohistochemical study revealed the immunoreactivity of these proteins in motor neurons. Double-fluorescence immunohistochemistry revealed the induction of RIP1 and RIP3, and that of Bax and caspase-8, in the same motor neurons., Conclusions: These data suggest that Nec-1 reduces delayed motor neuron death and attenuates delayed paraplegia after transient spinal cord ischemia in rabbits by selectively inhibiting necroptosis of motor neurons with minimal effect on their apoptosis., (Copyright © 2023. Published by Elsevier Inc.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on children's lifestyles. Some studies have reported psychological changes in children after the pandemic, but information on musculoskeletal problems is scarce. This study aimed to investigate the incidence of knee pain and changes in physical activity after the spread of COVID-19 among elementary and junior high school students in Japan., Methods: Knee pain and amount of physical activity were recorded on a monthly basis between August 2019 and February 2021 in children aged 8-14 years using a self-administered questionnaire. The amount of physical activity was scored using the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS). The period until February 2020 was defined as "Before pandemic," and the period from March 2020 was defined as "After pandemic." The incidences of knee pain and HSS Pedi-FABS scores before and after the COVID-19 pandemic were compared. Additionally, we compared the prevalence of knee pain and HSS Pedi-FABS scores according to sex and age., Results: We enrolled 886 and 881 participants before and after the pandemic, respectively. The prevalence of knee pain among the participants before and after the pandemic was 6.7% and 7.9%, respectively (p = 0.032). The mean HSS Pedi-FABS scores before and after the pandemic were 14.8 and 14.5, respectively (p = 0.005). Participants aged 14 years had a significantly lower incidence of knee pain (p = 0.013) and significantly higher HSS Pedi-FABS scores (p < 0.001) after the spread of COVID-19., Conclusions: In elementary and junior high school students, increase in the incidence of knee pain and decrease in the amount of physical activity after the spread of COVID-19 were observed., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Understanding the physiological effects of food ingredients on bodily functions is crucial for the development of foods for specified health use (FoSHU) and functional foods. To investigate this, intestinal epithelial cells (IECs) have been widely studied as they are most frequently exposed to the highest concentrations of food ingredients. Among the various functions of IECs, in this review, we have discussed glucose transporters and their involvement in preventing metabolic syndromes such as diabetes. Phytochemicals are also discussed, as they significantly inhibit glucose and fructose absorption via sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 5 (GLUT5), respectively. Additionally, we have focused on the barrier functions of IECs against xenobiotics. Phytochemicals induce detoxification of metabolizing enzymes via pregnane X receptor or aryl hydrocarbon receptor activation, which suggests that food ingredients can enhance barrier function. This review will provide insights into the role of food ingredients and glucose transporters, as well as detoxification metabolizing enzymes in IECs, and help guide future research on these aspects., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2023 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Secretoglobin (SCGB) 3A2 is a bioactive molecule exhibiting various functions such as improving allergic airway inflammation and pulmonary fibrosis and promoting bronchial branching and proliferation during lung development. To determine if and how SCGB3A2 is involved in chronic obstructive pulmonary disease (COPD), a multifactorial disease with both airway and emphysematous lesions, a COPD mouse model was created by exposing Scgb3a2-deficient (KO), Scgb3a2-lung-specific overexpressing (TG), and wild type (WT) mice to cigarette smoke (CS) for 6 months. The KO mice showed loss of lung structure under control condition, and CS exposure resulted in more expansion of airspace and destruction of alveolar wall than WT mouse lungs. In contrast, TG mouse lungs showed no significant changes after CS exposure. SCGB3A2 increased the expression and phosphorylation of signal transducers and activators of transcription (STAT)1 and STAT3, and the expression of α1-antitrypsin (A1AT) in mouse lung fibroblast-derived MLg cells and mouse lung epithelial-derived MLE-15 cells. In MLg cells, A1AT expression was decreased in Stat3-knockdown cells, and increased upon Stat3 overexpression. STAT3 formed a homodimer when cells were stimulated with SCGB3A2. Chromatin immunoprecipitation and reporter assays demonstrated that STAT3 binds to specific binding sites on the Serpina1a gene encoding A1AT and upregulates its transcription in lung tissues of mice. Furthermore, nuclear localization of phosphorylated STAT3 upon SCGB3A2 stimulation was detected by immunocytochemistry. These findings demonstrate that SCGB3A2 protects the lungs from the development of CS-induced emphysema by regulating A1AT expression through STAT3 signaling., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: To investigate differential clinical outcomes in patients treated with partial nephrectomy (PN) vs. percutaneous cryoablation (PCA) for cT1b renal tumors., Materials and Methods: We retrospectively analyzed the records of 119 patients who had undergone PN (n = 90) or PCA (n = 29) for cT1b renal tumors. Inverse probability weighting (IPW) was used for balancing patient demographics, including renal function and tumor complexity. Perioperative complications, renal function preservation rates, and oncological outcomes such as local recurrence-free, metastasis-free, cancer-specific, and overall survival were compared using IPW-adjusted restricted mean survival times (RMSTs)., Results: PCA was more likely to be selected for octogenarians (odds ratio: 11.4, 95% confidence interval [CI]: 3.33-45.1). During the median follow-up of 43 months in the PCA group and 36.5 months in the PN group, unablated local residue or local recurrence was noted in 6 patients in the PCA group and local recurrence was noted in 4 patients in the PN groups. Of the 6 patients in the PCA group, 4 underwent salvage PCA, and local control had been achieved at the last visit. In the IPW-adjusted population, PCA had significantly worse local recurrence-free survival compared with PN (IPW-adjusted RMST difference: -22.7 months, 95% CI: -45.3 to -0.4, P = 0.046). IPW-adjusted RMST for metastasis-free survival (P = 0.23), cancer-specific survival (P = 0.77), and overall survival (P = 0.11) did not differ between PCA and PN. In addition, PN was not a predictor for local control failure at the last visit (odds ratio: 0.30, 95%CI: 0.05-1.29). There were no statistically significant differences between PN and PCA in renal function preservation or overall/severe complication rates., Conclusions: In patients with cT1b renal tumor, although the local recurrence rate is higher for PCA than for PN, PCA provides comparable distant oncologic outcomes. PCA can be an alternative treatment option for elderly, comorbid patients, even those with cT1b renal tumors., Competing Interests: Conflicts of interest Takahiro Kimura is a paid consultant/advisor of Astellas, Bayer, Janssen and Sanofi. The other authors declare no conflicts of interest associated with this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: We examined outcome of acute ischemic stroke (AIS) with administration of antithrombotics within 24 h after intravenous low-dose alteplase., Methods: Consecutive AIS patients who were treated with intravenous alteplase at 0.6 mg/kg from 2005 to 2021 were retrospectively included in our single-center registry. Patients were classified into two groups: those who received antithrombotics within 24 h after intravenous alteplase (early initiation group) and those who did not (control group). Safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH (sICH) within 36 h after onset, and death within 3 months. sICH was defined as any ICH with a ≥ 4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score or death within 36 h., Results: Of 1111 patients (women, 426; median age, 76 [interquartile range, 69-83] years; median NIHSS score, 11 [6-19]; cardioembolism, 580 [52.2%]), early initiation group comprised 58 patients (22; 72 [65-80] years; 7 [4-12]; 11 [19.0%]) and control group comprised 1053 patients (404; 77 [69-84] years; 11 [6-19]; 569 [54.1%]). No significant between-group differences were observed in the incidence of any ICH (17.2% vs. 21.6%; adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 0.57-2.44), sICH (0% vs. 0.9%, P = 1.00), or death within 3 months (5.2% vs. 6.7%; aOR, 1.23; 95% CI, 0.36-4.23)., Conclusions: Early initiation of antithrombotics after intravenous alteplase at 0.6 mg/kg did not increase the rate of sICH or death within 3 months and may be used with caution in patients with advanced neurological deterioration., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Salivary glands are physiologically orchestrated by the coordinated balance between cell differentiation, proliferation, apoptosis, and interactions between epithelial, mesenchymal endothelial, and neuronal cells, and they are frequent sites of manifestations of Sjögren's syndrome (SS) or IgG4-related disease (IgG4-RD). However, little is known about salivary gland homeostasis and its involvement in those diseases. Inhibitor of DNA binding/differentiation 4 (Id4) is an Id protein involved in the transcriptional control of many biological events, including differentiation. Studies of Id4-deficient mice revealed that Id4-deficient submandibular glands were smaller and exhibited accelerated differentiation, compared with those from wild-type littermates. In addition, dry mouth symptoms and Th17 expansion in splenocytes were also observed in the absence of Id4. Furthermore, Id4 levels in the salivary glands of patients with IgG4-RD, but not SS, were significantly decreased compared with those of healthy controls. miRNA-mRNA integrated analysis demonstrated that miR-486-5p was upregulated in IgG4-RD patients and that it might regulate Id4 in the lesion sites. Together, these results provide evidence for the inhibitory role of Id4 in salivary differentiation, and a critical association between Id4 downregulation and IgG4-RD., 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)