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Sensorineural hearing loss is usually intractable because of virtually no capacity for hair cell (HC) regeneration in mammals. In contrast to mammals, lower vertebrates including birds have the capability for HC regeneration. Elucidation of precise mechanisms for HC regeneration in avian auditory epithelia will contribute to exploring key molecules for inducing HC regeneration in mammals. We previously established an explant culture model of the chick auditory epithelium, namely basilar papilla (BP), showing total HC loss and consecutive HC regeneration through direct conversion of supporting cells (SCs) to HCs (Matsunaga, 2020). Single-cell RNA sequencing using this model illustrated dynamic changes in expressed genes in BP SCs during direct conversion, which indicates that reprogramming of SCs to the precursor state occurs before differentiation into HCs (Matsunaga, 2023). To explore mechanisms of SC reprogramming toward hair cell regeneration in chick BP, we performed an integrated analysis of RNA- and ATAC-seq of chick BP explant cultures during the early phase (three time points) of HC regeneration. ATAC sequencing detected 80,366 peaks. Based on the distance from the transcription start site, and correlations between read counts and peak depths and between their alterations in a time course, we determined enhancer candidate loci for differentially expressed genes. We focused on a set of temporally upregulated genes during SC reprogramming in our previous single-cell RNA sequencing data (Matsunaga, 2023). In temporally upregulated genes during SC reprogramming, enhancer candidate loci were identified in nine genes. Motif enrichment analysis of these loci indicated transcription factors that may control chromatin remodeling in SC reprogramming. In the near future, we will examine spaciotemporal expression patterns of these transcription factors in regenerating chick BP. [ABSTRACT FROM AUTHOR]

Background and Objective: Surgical site infection (SSI) is common in surgery for malignant musculoskeletal tumours, specifically those arising from the trunk. In this study, we investigated the risk factors for SSI after resection of musculoskeletal tumours of the trunk., Methods: This retrospective observational study included 125 patients (72 males, 53 females) with musculoskeletal tumours of the trunk in our hospital from 1 April 2008 to 31 August 2023. The incidence of SSI and its risk factors were investigated., Results: SSI was observed in 26% (32/125), and the median time to SSI was 22 days. On multivariate analysis, the following were identified as risk factors for SSI: tumours arising caudal to Jacoby's line (hazard ratio [HR] 4.04; P = .0107), soft tissue reconstruction (HR 3.43; P = .0131), and low Geriatric Nutritional Risk Index (GNRI) (HR 0.96; P = .0304). Patients were classified into two risk categories based on GNRI scores: the risk group (GNRI ≤98) and no risk group (>98). The risk group showed a significantly lower overall noninfection survival rate (P = .023)., Conclusion: Tumours arising caudal to Jacoby line, soft tissue reconstruction, and lower GNRI were risk factors for SSI. Preoperative and postoperative nutritional interventions should be considered to improve GNRI., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Trunk rotation during pitching correlates with pitching velocity and load on the joints of the upper limb. Trunk rotation is often focusing on during teaching the pitching motion. Athletes who exhibit early trunk rotation during pitching often have low thoracic spine rotational range of motion. The purpose of this study was to investigate the relationship between the range of thoracic spine rotation measured using the lumbar locked rotation test (LLR-t), hip-shoulder separation (H/S) and thoracic rotation angle at stride foot contact (SFC), and ball velocity., Study Design: Descriptive laboratory study., Methods: Fifteen healthy male high school students belonging to a baseball club were recruited for participation. The throwing side and non-throwing side LLR-t was performed using an inclinometer. Hip-shoulder separation and thoracic rotation angle during SFC were measured using a pitching motion analysis application: Pitch AI. In addition, a tracking device specifically designed for pitching：Pitching2.0 was employed to measure ball velocity. Correlations between LLR angle, H/S, trunk rotation angles at SFC, and ball velocity were examined using Pearson's correlation coefficient., Result: There was a positive correlation（r=0.52，p=0.047） between the LLRt angle and H/S. Additionally, there was a negative correlation（r=-0.62, p =0.01） between the LLRt angle on the throwing side and thoracic rotation angle. There was a positive correlation(r=0.54, p=0.04) between ball velocity and H/S and a negative correlation(r=-0.56, p=0.03) between ball velocity and thoracic rotation angle during SFC. 　., Conclusion: The LLR-t measures thoracic rotation angle with the pelvis-lumbar spine fixed. The results indicated that throwing side LLR was related to the thoracic angle during SFC and hip-shoulder separation., Level of Evidence: 3., Competing Interests: The authors report no conflicts of interest., (© The Author(s).)

Objective: Wound dehiscence following craniotomy is a complication for which patients are subjected to additional procedures to achieve wound closure. During surgery for epilepsy, a craniotomy is performed at various sites to cure or palliate seizures in patients with intractable epilepsy. Collaborations between medicine and engineering have provided many surgical devices and materials for various stages of craniotomy, from skin incision to wound closure. The risk factors for wound dehiscence remain undetermined. Here, the authors attempt to identify risk factors associated with wound dehiscence after surgery for epilepsy., Methods: They retrospectively reviewed the clinical records and operative notes of consecutive patients with intractable epilepsy who had undergone craniotomy to allow resective or disconnective surgery between 2015 and 2023 in the Department of Neurosurgery, Hiroshima University Hospital, and had a minimum follow-up of 1 year. The authors conducted a multivariate logistic regression analysis to determine the risk factors for wound dehiscence., Results: The study population comprised 174 patients who had undergone corpus callosotomy (70 patients), cortical resection (CR; 65 patients), or CR via intracranial video electroencephalography monitoring (IVEEG; 39 patients). Wound dehiscence occurred in 14 patients (8.0%). Univariate analysis showed that wound dehiscence was associated with CR via IVEEG (p = 0.0330), electrocautery scalpels (p = 0.0037), T-shaped skin incisions (p = 0.0216), dural closure (p = 0.0002), and longer operative duration (p = 0.0088). Multivariate logistic regression analysis revealed that skin incision using an electrocautery scalpel (p = 0.0462, OR 9.38, 95% CI 1.04-84.74) and dural closure using nonabsorbable artificial dura (p = 0.0078, OR 6.29, 95% CI 1.63-24.31) were independent risk factors for wound dehiscence., Conclusions: Surgical devices and materials contribute to wound dehiscence after epilepsy surgery. To avoid wound dehiscence, the use of an electrocautery scalpel is not recommended when performing skin incisions, nor is dural closure using a nonabsorbable artificial dura.

Background: Utilizing interictal manifestations for the diagnosis of epilepsy is challenging. We investigated whether an interictal "head-turning sign," typically indicative of dependence on others observed in Alzheimer's disease, can act as a behavioral marker of idiopathic generalized epilepsy., Methods: This multicenter study examined 579 consecutive patients, with a mean age of 36.8 ± 20.4 years, who did not have an intellectual disability and had their first outpatient visit for epilepsy evaluation between 2019 and 2023. Patients were categorized into IGE, non-IGE epilepsy, non-epileptic, and psychiatric conditions based on their ultimate diagnostic outcomes to identify difference of the occurrence of the head-turning sign among them. Additionally, we extracted data from patients under the age of 40, specifically adolescents and young adults (AYA). Then we used propensity score matching to confirm the reproducibility of observed differences and to identify associated factors within the AYA age group., Results: The occurrence of the head-turning sign was significantly more prevalent in the IGE group compared to the non-IGE group (20.4 % vs. 2.2 %; P<0.0001) and non-epileptic group (20.4 % vs. 8.3 %; P=0.033). Following the matching, the head-turning sign was still evident in IGE relative to non-IGE patients (14.6 % vs. 4.5; P=0.004), yielding a 94 % specificity for IGE. IGE diagnosis (P<0.0001), myoclonic seizure (P<0.0001), being visited by a parent (P=0.017), and comorbidity with headache (P=0.021) were significantly associated with the head-turning sign. Multivariate analysis revealed that IGE (odds ratio: OR=2.80, P=0.028), attending with a parent (OR=2.92, P=0.029), and comorbidity with headache (OR=4.06, P=0.016) were independently associated with the head-turning sign., Conclusions: We confirmed a substantial association between the interictal "head-turning sign" and IGE. This unique sign may reflect a tendency towards dependence on others in IGE, and may serve as a promising diagnostic auxiliary marker for identifying IGE in the AYA age group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Computed tomography angiography (CTA) was performed under general anaesthesia on a 7-month-old toy poodle that was referred with the chief complaints of salivation and neurological symptoms. The CTA revealed a rare form of posthepatic portosystemic shunt (PSS) via the suspected persistent left umbilical vein communicating with the internal thoracic vein in addition to an azygos continuation of the caudal vena cava (CVC). The patient underwent surgery for partial ligation of PSS on Day 4 after the initial examination. On Day 71, after the initial examination, a second surgery was performed for complete ligation. Approximately 10 years have passed since the patient's second surgery, and he is still healthy, and generally in good condition. Although the morphology of the shunt in this case was unusual and was accompanied by an azygos continuation of the CVC, a favourable course of treatment was obtained by ligating the shunt vessel. This case report suggests that CTA can reveal the complex morphological characteristics like our case. Surgical treatment in this case resulted in favourable progress, similar to that in dogs with commonly observed extrahepatic PSS., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Objective Exercise therapy as part of cardiac rehabilitation is one of the most effective treatments for patients with chronic heart failure (HF). The anaerobic threshold (AT) determined by an exhaled gas analysis during cardiopulmonary exercise testing (CPX) is used to prescribe the appropriate level of exercise therapy. However, CPX using an exhaled gas analysis is not widely performed because of its cost, complexity, and the need for skilled staff. Therefore, a simpler and inexpensive method for determining AT without respiratory gas measurements is required in patients with HF. The present study elucidated the relationship between the AT determined by the CPX ventilatory method (CPX-AT) and the AT determined by cardiac acoustic biomarkers (CABs), which are measured by acoustic cardiography (CAB-AT), in HF patients. Methods Patients underwent symptom-limited ramp CPX twice using a cycle ergometer. The ATs determined from the exhaled gas analysis were identified by three independent physicians. CABs, including the first heart sound (S1) and the second heart sound intensities (peak-to-peak amplitudes), electromechanical activation time (EMAT) defined as the time interval from the Q wave onset on electrocardiography to S1, heart rate, and other parameters, were collected during CPX. Patients Forty patients with HF were included in this study. Results A significant correlation (R=0.70; p<0.001) was found between CPX-AT and CAB-AT, using the double product of S1 intensity and heart rate. CAB-AT using S1 intensity also showed a significant correlation with CPX-AT (R=0.71; p<0.001). Conclusion The present study suggests a possible new method for determining AT without respiratory gas measurements in patients with HF.

Purpose: This study investigated whether the oral vasopressin V 2 receptor antagonist tolvaptan has beneficial effects on mortality in real-world congestive heart failure (CHF) patients with hypoperfusion (i.e. the wet-cold pattern), from the viewpoint of cardiorenal syndrome., Methods: Data on 5511 consecutive CHF patients were extracted from the Tokyo CCU Network data registry. Congestion and hypoperfusion were defined by Nohria-Stevenson clinical profiles at the time of hospitalization. Propensity scores for tolvaptan use were calculated for each patient and used to assemble two matched cohorts of patients receiving tolvaptan or not in the CHF with and without hypoperfusion groups., Results: Of the entire study cohort, 1073 patients (19%) had CHF with hypoperfusion (i.e. the wet-cold pattern). In-hospital mortality was significantly higher for CHF patients with than without hypoperfusion (log-rank, P < 0.001). The rate of tolvaptan use did not differ significantly between CHF patients with and without hypoperfusion (15% vs. 14%, respectively; P = 0.7848). In the propensity-matched CHF with hypoperfusion cohort, there was a significant association between the use of tolvaptan and a reduction in in-hospital mortality (log-rank, P = 0.0052). Conversely, in the matched CHF without hypoperfusion cohort, tolvaptan use was not associated with in-hospital mortality (log-rank, P = 0.4417)., Conclusion: There was a significant association between the use of tolvaptan and a reduction in in-hospital mortality in CHF patients with, but not without, hypoperfusion. These findings hint at possible individualized therapies for patients with CHF., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The 2HELPS2B score is an invaluable tool for assessing seizure risk in critically ill patients with unconsciousness. However, this can be challenging for non-epileptologists to use owing to its reliance on electroencephalogram (EEG) analysis. Thus, identifying clinical manifestations associated with high 2HELPS2B scores is crucial., Methods: We examined patients who underwent EEG for acute impaired consciousness in the emergency department between 2020 and 2022. We evaluated the clinical manifestations immediately prior to the EEG tests and identified those associated with a 2HELPS2B score ≥ 2. Additionally, we investigated clinical outcomes in accordance with these manifestations and the 2HELPS2B score., Results: A total of 78 patients were included in this study. While the median 2HELPS2B score was 1 (range: 0-6), 13 patients (16.6%) showed electrographic/electroclinical seizures or status epilepticus and 16 patients (20.5%) showed ictal-interictal continuum in their EEGs. Abnormal muscle tonus (p = 0.034) and eye deviation (p = 0.021) were Significantly associated with a 2HELPS2B score ≥ 2. The presence of these manifestations (p < 0.001) and a 2HELPS2B score ≥ 2 (p < 0.001) were both significantly associated with a favorable response to anti-seizure medication. Conversely, patients with a 2HELPS2B score ≥ 2 who exhibited these clinical manifestations were more likely to be non-dischargeable (p = 0.053), have prolonged intensive care unit stays (p = 0.002), or require extended ventilator use (p = 0.082)., Conclusion: Abnormal muscle tonus and eye deviation were significant manifestations compatible with a 2HELPS2B score ≥ 2 and may indicate an increased risk of seizures or the severity of the epileptic condition., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there are no conflicts of interest to disclose, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Real-world data on health-related quality of life (HRQoL) in advanced urothelial carcinoma (aUC) receiving immune checkpoint inhibitors (ICIs) are limited. This study included 42 patients with aUC who received second-line or later pembrolizumab (n = 19), maintenance avelumab followed by first-line chemotherapy (n = 13), or adjuvant nivolumab after radical surgery (n = 10). Time-course changes in the domains and scales related to HRQoL were evaluated using the EORTC QLQ-C30, FACT-G, and SF-8 questionnaires during ICI therapy. Anchor-based approaches for minimally important differences were determined as 'improved', 'stable', and 'deteriorated'. We found significant improvements after the start of pembrolizumab treatment on many scales. Almost none of the scales changed significantly in the avelumab and nivolumab groups. Approximately 80% of the pembrolizumab group had deteriorated social/family well-being in FACT-G. Approximately 60% of the patients in the avelumab group had deteriorated general health and vitality in SF-8. In the nivolumab group, none of the scales deteriorated in > 50% of the patients. Deterioration of physical function in the SF-8 was associated with occurrence of treatment-related adverse events ≥ grade 2 during ICI therapy (P = 0.013). Our findings demonstrated that majority of patients with aUC who received ICI therapy had a stable HRQoL, which was consistent with evidence from clinical trials., (© 2024. The Author(s).)

Iron-based 1111-type superconductors display high critical temperatures and relatively high critical current densities J c . The typical approach to increasing J c is to introduce defects to control dissipative vortex motion. However, when optimized, this approach is theoretically predicted to be limited to achieving a maximum J c of only ∼30% of the depairing current density J d , which depends on the coherence length and the penetration depth. Here we dramatically boost J c in SmFeAsO 1-x H x films using a thermodynamic approach aimed at increasing J d and incorporating vortex pinning centres. Specifically, we reduce the penetration depth, coherence length and critical field anisotropy by increasing the carrier density through high electron doping using H substitution. Remarkably, the quadrupled J d reaches 415 MA cm -2 , a value comparable to cuprates. Finally, by introducing defects using proton irradiation, we obtain high J c values in fields up to 25 T. We apply this method to other iron-based superconductors and achieve a similar enhancement of current densities., (© 2024. The Author(s).)

Purpose: This study investigated differences in the migration of meniscus sutured with pull-out sutures for treating medial meniscus posterior root tears (MMPRTs) according to the bone tunnel position, using cadaveric knees., Methods: Six knees of three donors fixed using Thiel's method were included in this study. The MMPRTs were created, and a single suture was performed at the torn meniscus using an arthroscopic procedure. The suture was pulled out through the tibial bone tunnel, and the meniscus displacement was measured as the change in length during 0-120° of knee flexion. Three types of bone tunnels (anatomical, anterior and posterior) were created for each knee, and the sutures were pulled out of each tunnel three times. After completing all measurements, the proximal tibia was extracted and micro-computed tomography was performed to evaluate the tunnel position., Results: A significantly smaller change in suture length was observed in the posterior group compared to the other two groups (anatomical group, 5.17 ± 1.8 mm; anterior group, 7.50 ± 3.2 mm; posterior group, 1.17 ± 1.0 mm; p  > 0.01). In addition, a significant correlation between the anteroposterior tunnel position and suture length change was observed ( r  = -0.720; p  = 0.001)., Conclusions: When pull-out sutures were used to repair MMPRTs, the suture length change was approximately 5 mm during knee flexion and extension when the bone tunnel was located at the anatomical attachment site. This change was larger when the tunnel position was anterior, and smaller when the tunnel position was posterior., Level of Evidence: LEVEL Ⅲ case-control 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.)

Aim: Some patients undergoing liver resection for hepatocellular carcinoma (HCC) have poor outcomes. Therefore, we aimed to propose a new resectability classification for patients with HCC., Methods: We classified patients into three categories: resectable (R), borderline resectable (BR), and unresectable (UR). Patients (n = 409) who underwent hepatectomy for HCC were assigned to the non-UR (R and BR classes combined; n = 285) and UR-HCC classes (n = 68; training cohort). Patient characteristics in the BR-HCC and R-HCC groups were compared. The new criteria were tested in a validation cohort (n = 295)., Results: Of the 285 patients, 229 and 56 were classified into the R- and BR-HCC classes, respectively, using macrovascular invasion, tumor size, and future liver remnant/modified albumin-bilirubin scores. Patients with BR-HCC demonstrated significantly worse progression-free and overall survival (p < 0.0001 and p < 0.0001, respectively) than patients with R-HCC in the training cohort. Similar results were observed in the validation cohort. Multivariate analysis of the non-UR-HCC group in the training cohort revealed that the tumor number and BR-HCC were independent predictive factors for poor overall survival., Conclusions: This classification can help select patients with BR-HCC for preoperative treatment before considering surgery., (© 2024 The Author(s). Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia with a poor prognosis. In this study, we established a novel murine AEL model with Trp53 depletion and ERG overexpression. ERG overexpression in Trp53-deficient mouse bone marrow cells, but not in wild-type bone marrow cells, leads to AEL development within two months after transplantation with 100% penetrance. The established mouse AEL cells expressing Cas9 can be cultured in vitro, induce AEL in vivo even in unirradiated recipient mice, and enable efficient gene ablation using the CRISPR/Cas9 system. We also confirmed the cooperation between ERG overexpression and TP53 inactivation in promoting the growth of immature erythroid cells in human cord blood cells. Mechanistically, ERG antagonizes KLF1 and inhibits erythroid maturation, whereas TP53 deficiency promotes proliferation of erythroid progenitors. Furthermore, we identified HDAC7 as a specific susceptibility in AEL by the DepMap-based two-group comparison analysis. HDAC7 promotes the growth of human and mouse AEL cells both in vitro and in vivo through its non-enzymatic functions. Our study provides experimental evidence that TP53 deficiency and ERG overexpression are necessary and sufficient for the development of AEL and highlights HDAC7 as a promising therapeutic target for this disease., (© 2024. The Author(s).)

Purpose: Sagging eye syndrome (SES), esotropia with high myopia including heavy eye syndrome, and age-related esotropia (ARE)-collectively termed orbital pulley degeneration syndrome (OPDS)-are characterized by strabismus with orbital pulley lateral rectus-superior rectus band impairment. Herein, we examined body mass index (BMI) in OPDS to determine SES-associated anthropometric characteristics., Design: Retrospective cohort study., Methods: We compiled and analyzed the BMI of patients aged ≥50 years who underwent strabismus surgery at a single center in Shizuoka, Japan, between July 2020 and March 2023. BMI (kg/m 2 ) was categorized into 4 groups: <18.5, 18.5 to 21.9, 22 to 24.9, and ≥25. As the boundary between OPDS and SES is ambiguous, we assumed a pure SES group by excluding patients with ARE and esotropia with high myopia from the OPDS group. Overall, 204 patients (age: 67.7 ± 9.7 years) were included in the study., Results: There were 78/126 and 49/119 patients in the OPDS/non-OPDS and SES/non-SES groups (age: 70.4 ± 9.5/66.0 ± 9.6 years, P = .002 and 75.0 ± 6.0/66.6 ± 9.5 years, P < .001; BMI: 21.2 ± 3.3/23.2 ± 3.0 kg/m 2 , P < .001 and 21.2 ± 3.3/23.1 ± 3.0 kg/m 2 , P = .003), respectively. In the BMI-stratified analysis, OPDS and SES were more prevalent in the <18.5 BMI group than in the 22 to 24.9 and ≥25 BMI groups (P < .001 and P = .006, respectively). Logistic regression analysis, adjusted for age and sex, showed that lower BMI was associated with a higher prevalence of OPDS and SES., Conclusions: Patients with OPDS, including SES, had lower BMI than other patients with strabismus. Therefore, BMI may be a clinical clue to SES., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Maintenance avelumab is currently recommended for patients with unresectable and/or metastatic (mUC) achieving at least stable disease (SD) on first-line platinum-based chemotherapy (1L-CT). Pembrolizumab is an alternative therapeutic avenue for this patient cohort in clinical practice. We investigated real-world data, focusing on the correlation between response to 1L-CT and oncological efficacy of subsequent immune checkpoint inhibitor (ICI) therapy with avelumab or pembrolizumab., Methods: A multicenter database registered 626 patients with mUC diagnosed from 2008-2023; among these, 175 receiving 2-6 cycles of 1L-CT followed by ICI therapy. Patients were categorized based on response to 1L-CT using the Response Evaluation Criteria in Solid Tumors (v1.1). Objective response rate on ICI, progression to ICI-free survival (ICI-PFS), and overall survival from start of 1L-CT were compared between avelumab-treated and pembrolizumab-treated patients in each response subgroup., Results: ICI-PFS was significantly longer in patients achieving partial response on 1L-CT and subsequently receiving pembrolizumab compared to those receiving avelumab. Notably, patients achieving SD on 1L-CT and subsequently receiving pembrolizumab manifested significantly higher objective response rate (14% and 41%, respectively) and prolonged ICI-PFS relative to those receiving avelumab. In contrast, overall survival did not delineate difference between patients treated with avelumab versus pembrolizumab. Similar findings were discerned in the subanalysis of patients having favorable SD (tumor shrinkage, from - 29 to 0%) and unfavorable SD (tumor enlargement, from + 1 to + 19%) on 1L-CT., Conclusions: Our study provides real-world evidence regarding difference of oncological efficacy between maintenance avelumab and subsequent pembrolizumab in patients with mUC who achieved partial response or SD on 1L-CT., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Crush syndrome, which frequently occurs in earthquake disasters, often leads to rhabdomyolysis induced acute kidney injury (RIAKI). Recent findings indicate that systemic inflammatory response syndrome (SIRS) exacerbates muscle collapse, contributing to RIAKI. The purpose of this study is to investigate the involvement of multiple site inflammation, including intraperitoneal, in crush syndrome. In a mouse model of RIAKI, elevated levels of inflammatory mediators such as TNFα, IL-6, myoglobin, and dsDNA were observed in serum and the peritoneal cavity, peaking earlier in the intraperitoneal cavity than in serum or urine. Our previously developed novel peptide inhibiting leukocyte extracellular traps was administered intraperitoneally and blocked all of these mediators in the intraperitoneal cavity and serum, ameliorating muscle damage and consequent RIAKI. Although further studies are needed to determine whether intraperitoneal inflammation associated with muscle collapse can lead to systemic inflammation, resulting in more severe and prolonged muscle damage and renal injury, early suppression of multiple site inflammation, including intraperitoneal, might be an effective therapeutic target., Competing Interests: The authors applied for a patent “Peptides having inhibitory activity on leukocyte extracellular trap formation” (International Application No. PCT/JP2022/042111). The authors declare that they do not have any other competing interests., (Copyright © 2024 Miyauchi, Okubo, Iida, Kawakami, Takayama, Hayashi, Haruta, Sasaki, Hayashi and Hirahashi.)

The main cause of acute coronary syndrome (ACS) is plaque rupture and thrombus formation. However, it has not been fairly successful to identify vulnerable plaque to rupture using conventional parameters of intravascular imaging modalities. Fractal analysis is one of the mathematical models to examine geometrical features of picture image using a specific parameter called as fractal dimension (FD) which suggests geometric complexity of the image. This study examined FD of the optical coherence tomography (OCT)-derived images of the culprit plaque in patients with ACS vs stable angina pectoris (SAP) to evaluate the feasibility of FD for identifying vulnerable coronary plaques prone to provoke ACS distinguished from stable plaques only provoking SAP. We examined 65 cases (34 ACS patients, 31 SAP patients) in which the culprit lesion was imaged by OCT before percutaneous coronary intervention in patients with ACS and SAP. The culprit plaque lesion in the ACS group had a significantly larger mean lipid arc (203.8 ± 39.4° vs 152.3 ± 34.5°, p < 0.001) and a larger lipid plaque length (12.6 ± 5.1 mm vs 7.7 ± 2.7 mm, p < 0.001) and a thinner fibrous cap thickness (75.3 ± 22.3 μm vs 134.8 ± 53.2 μm, p < 0.001) than those in the SAP group. The prevalence of OCT-derived macrophage infiltration (Mph) in the entire culprit coronary vessel as well as that of the OCT-derived thin-cap fibroatheroma (TCFA) at the culprit lesion were significantly greater in the ACS group than those in the SAP group, respectively (Mph: 61.8% vs 35.5%, p = 0.048; TCFA: 44.1% vs 6.4%, p < 0.001). The FD of culprit plaque in the ACS group was significantly greater than in the SAP group (2.401 ± 0.073 vs 2.341 ± 0.051, p < 0.001). In multivariate regression analysis, the presence of Mph was a significant determinant of FD (regression coefficient estimate 0.049, CI 0.018-0.079, p = 0.002). The FD of OCT-derived image of culprit coronary plaque in the ACS group was significantly greater than that in the SAP group, indicating that the culprit plaque in ACS were structurally more complex. Therefore, fractal analysis of coronary OCT images might be clinically useful for identifying coronary plaques prone to provoke ACS., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

In this study, we aimed to investigate the antimicrobial susceptibility of Staphylococcus saprophyticus in Japan. Additionally, we evaluated the effectiveness of different therapeutic agents and compared the differences in their outcomes in treating S. saprophyticus-induced acute cystitis, considering that cephem antibiotics are standard treatments for acute cystitis in Japan. This retrospective study was conducted at ten hospitals housing urology departments, where urologists were dispatched from the Department of Nephro-Urology, Nagoya City University Graduate School of Medicine. Initially, we prepared a list of S. saprophyticus cases detected between January 2012 and December 2021, using the bacteriological testing system of each hospital. Subsequently, we reviewed the electronic medical records of the listed cases to investigate the causative diseases, treatments, and outcomes in patients with acute cystitis. The number of S. saprophyticus samples collected in this study was 289 from urine specimens, including 157 from women with acute cystitis. All antimicrobial agents demonstrated good therapeutic efficacy in all patients, except in those who did not return for follow-up visits (30 %). Furthermore, only one case of inadequate therapeutic efficacy was observed in a patient treated with a third-generation cephalosporin. All the other patients were cured. These findings revealed that the susceptibility of S. saprophyticus to different antimicrobials did not differ considerably between the specimens from patients with acute cystitis and those from other patients, suggesting a similar trend of therapeutic efficacies of the tested antimicrobials against S. saprophyticus-induced acute cystitis., (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.)

Purpose: To evaluate the efficacy of surgical treatment of the discoid lateral meniscus with osteochondritis dissecans (OCD) through clinical and radiological evaluations, focusing on recurrent or postoperative OCD occurrence., Methods: This retrospective study included patients with symptomatic discoid lateral meniscus with OCD (pre-OCD group) and without OCD (non-OCD group) who had undergone arthroscopic surgery with >5 years of follow-up. Age, sex, Lysholm score, Tegner activity scale, surgical procedure, and recurrent or postoperative OCD lesions were compared. The association between patient variables and postoperative OCD was determined using multivariate logistic regression analysis., Results: Of the 95 knees, 15 (15%) were in the pre-OCD group. Healing was observed in 14/15 (93%) knees. Recurrent and postoperative OCDs were reported in 4/15 (28.5%) knees in the pre-OCD and 7/80 (8.8%) knees in the non-OCD groups at a mean of 3.2 ± 1.1 and 3.7 ± 1.2 years, respectively. Pre- and postoperative Tegner activity scale and Lysholm scores were higher in the pre-OCD group but similar to those in the non-OCD group. The incidence of recurrent OCD in the pre-OCD group was significantly higher than that of postoperative OCD in the non-OCD group. Younger patients (odds ratio, 0.49; p = 0.003) had an increased risk of experiencing recurrent or postoperative OCD in multivariate analysis. The optimal cutoff age for distinguishing recurrent or postoperative OCD was 9 years., Conclusion: Surgical procedures for OCD lesions in the pre-OCD group were successful. Multivariate analysis identified age as a risk factor for recurrent or postoperative OCD; therefore, conservative treatment is recommended for patients with discoid lateral meniscus before preadolescence to prevent postoperative OCD occurrence., Level of Evidence: Level III., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: Uremic toxin indoxyl sulfate (IS) induces vascular inflammation, a crucial event in renal failure, and vascular complications in patients with chronic kidney disease (CKD). In endothelial cells, IS increases the production of inflammatory cytokines partially via the activation of the aryl hydrocarbon receptor (AhR), and several food flavonoids have been reported to act as antagonists of AhR., Objective: This study aimed to investigate whether antagonistic flavonoids can attenuate IS-induced inflammatory responses in vascular endothelial cells in vitro and renal failure in vivo ., Design: Human umbilical vein endothelial cells (HUVECs) pretreated with the flavones apigenin, chrysin, or luteolin were stimulated with IS. Expression levels of genes involved in AhR signaling, inflammatory cytokine production, and reactive oxygen species (ROS) production were analyzed. Uninephrectomized mice were orally administered chrysin and received daily intraperitoneal injections of IS for 4 weeks., Results: In HUVECs, IS upregulated the mRNA expression of AhR-targeted genes ( CYP1A1 and AhRR ), and genes involved in inflammation ( NOX4 , MCP-1 , IL-6, and COX2 ) and monocyte invasion/adhesion ( ICAM1 ). All three flavones attenuated the IS-induced increase in the expression of these mRNAs. They also suppressed the IS-induced nuclear translocation of AhR and intracellular ROS production. Furthermore, IS-induced phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was inhibited by treatment with these flavones. The results of in-vivo experiments showed that administration with chrysin attenuated the elevation of blood urea nitrogen levels and AhR-target gene expression and the pathological impairment of renal tissues in mice, regardless of higher serum levels of IS., Conclusions: Natural food flavones antagonizing AhR exerted protective effects against IS-induced inflammation through the inhibition of the AhR-STAT3 pathway in HUVECs. Moreover, chrysin ameliorated IS-induced renal dysfunction in a mouse model of CKD. These flavonoids could be a therapeutic strategy for vascular inflammation in CKD., Competing Interests: The authors declare no potential conflicts of interest. This work was supported by JSPS KAKENHI, Grant Number JP21K19701, and Grant-in-Aid for JSPS Fellows, Grant Number JP21J15034, from the Japan Society for the Promotion of Science., (© 2024 Tomomi Iwashima et al.)

Introduction: Avelumab (Ave) is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to Ave treatment of mUC patients., Methods: A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with Ave (n = 43) because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n = 29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to Ave maintenance therapy as Ave-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the Geriatric Nutritional Risk Index (GNRI) for determining patients suitable for Ave, were evaluated., Results: The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4-not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5-NR) with tolerable adverse events. The cut-off values of prognostic factors were set by the receiver operating characteristic curve. Low age and GNRI sustainability were revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis., Conclusion: In mUC, Ave maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as a biomarker to predict being Ave-suitable., (© 2024 S. Karger AG, Basel.)

Purpose: Surgery could regain the ability to walk even in non-ambulatory patients with spinal cord compression due to metastatic spine disease. However, many patients cannot reach the stage of independent ambulation because most are at an advanced disease stage. This study investigated the regained independent ambulation rate after surgery and prognostic factors for independent ambulation after metastatic spinal cord compression surgery., Methods: In a retrospective cohort study, 38 non-ambulatory patients with spinal metastases at the cervical or thoracic lesions, who underwent surgery, were included. All surgeries were performed using laminectomy and posterior fixation. Recovery rates of independent ambulation and its prognostic factors were examined. Independent ambulation was defined as the use of a walking aid without wheelchair requirement. Factors, including age, tumor type, visceral organ metastasis, past systematic cancer therapy, neurological grade, the time from leg-symptom onset to non-ambulatory stage, and the time from non-ambulatory stage to surgery, were investigated., Results: The regained independent ambulation rate was 18% (7/38). Compared to non-ambulatory patients, those who regained independent ambulation were more likely to have less past systematic therapy (14% [1/7] vs. 74% [23/31], P=0.003) and slow paralysis progression (over seven days from leg-symptom onset to non-ambulatory stage) (86% [6/7] vs. 23% [7/31], P=0.002)., Conclusions: Recovery to independent ambulation in non-ambulatory patients with metastatic spinal cord compression was poor, even if surgery was performed. Absence of past systematic therapy and slow paralysis progression were favorable factors for regaining independent ambulation., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Kyushu University Institutional Review Board issued approval 22098-00. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iida et al.)

As the sizes of noble metal catalysts, such as platinum, have been successfully minimized, fundamental insights into the electronic properties of metal sub-nanoclusters are increasingly sought for optimizing their catalytic performance. However, it is difficult to rationalize the catalytic activities of metal sub-nanoclusters owing to their more complex electronic structure compared with those of small molecules and bulky solids. In this study, the adsorption of molecular oxygen on a Pt 13 sub-nanocluster supported on a graphene layer was analyzed using density functional theory. Unlike bulk Pt, the Pt 13 sub-nanocluster has multiple adsorption sites, and the adsorption energy depends strongly on the type of adsorption site. The O 2 adsorption energy does not correlate with the transferred charge between O 2 and the Pt 13 moiety; therefore, to elucidate the differences in the adsorption sites, we propose an original approach for analyzing the electronic structure change in metal sub-nanoclusters caused by molecular adsorption. Our analysis of the integrated local density of state (LDOS) revealed that O 2 adsorption on the Pt 13 sub-nanocluster has a distinct feature, different from that on a smaller Pt 2 cluster or rather a larger Pt slab. The change in the electronic structure of the Pt 13 moiety was primarily observed near the Fermi level, different from that of the Pt slab whose DOS was distributed over a wide energy range. Furthermore, the change in the integrated LDOS correlated well with the O 2 adsorption energy on the Pt 13 sub-nanocluster.

Background/objective: Cartilage oligomeric matrix protein (COMP) has utility as a diagnostic marker for osteoarthritis (OA). Our previous study revealed that the serum COMP level can be used to detect early cartilage change in non-OA patients with anterior cruciate ligament (ACL)-deficiency. However, there are still no studies on detecting the progression of cartilage degeneration in early OA. The aim of present study was to investigate whether serum COMP can detect the progression of cartilage degeneration after ACL reconstruction in non-OA patients., Methods: Patients without cartilage degeneration of early OA at ACL reconstruction and whose serum COMP levels could be measured were included in the study. Cartilage degeneration of early OA were defined as International Cartilage Repair Society (ICRS) grade 1 to 4 in more than 2 compartments or ICRS grade 2 to 4 in 1 compartment. The patients were divided into two groups: those who had cartilage degeneration of early OA at second-look arthroscopy (cartilage degeneration progression group) and those who did not (non-progression group), and the serum COMP values between the two groups were compared., Results: Thirty-one patients were included. There were 8 cases (25.8 %) in progression group and 23 cases (74.2 %) in non-progression group. There were significant differences between the two groups regarding age and change in serum COMP level. In terms of the rate of change in COMP, an increase of more than 1.24-fold was the cut-off value for detecting the progression of cartilage degeneration., Conclusions: In this study, the increase in serum COMP levels was significantly greater in progressed cartilage degeneration group than non-progression group after ACL reconstruction. Longitudinal serum COMP measurement could detect the progression of cartilage degeneration., Level of Evidence: Level Ⅲ, retrospective comparative study., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (© 2024 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

Background: AT-rich interaction domain 1A (ARID1A) has been proposed as a new biomarker for predicting response to immune checkpoint inhibitors (ICIs). The predictive value of ARID1A for predicting ICI effectiveness has not been reported for endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts ICI effectiveness for endometrial cancer treatment., Methods: We evaluated ARID1A expression, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunostaining endometrial samples from patients with endometrial cancer. Samples in which any of the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) were determined to be negative via immunostaining were excluded. In the ARID1A-negative group, microsatellite instability (MSI) status was confirmed via MSI analysis., Results: Of the 102 samples investigated, 25 (24.5%) were ARID1A-negative. CD8 and PD-1 expression did not differ significantly between the ARID1A-negative group and the ARID1A-positive group; however, the ARID1A-negative group showed significantly lower PD-L1 expression. Only three samples (14.2%) in the ARID1A-negative group showed high MSI. Sanger sequencing detected three cases of pathological mutation in the MSH2-binding regions. We also established an ARID1A-knockout human ovarian endometriotic epithelial cell line (HMOsisEC7 ARID1A KO), which remained microsatellite-stable after passage., Conclusion: ARID1A negativity is not suitable as a biomarker for ICI effectiveness in treating endometrial cancer.

Single-cell RNA-sequencing (scRNA-seq) technology has provided significant insights into cancer drug resistance at the single-cell level. However, understanding dynamic cell transitions at the molecular systems level remains limited, requiring a systems biology approach. We present an approach that combines mathematical modeling with a pseudotime analysis using time-series scRNA-seq data obtained from the breast cancer cell line MCF-7 treated with tamoxifen. Our single-cell analysis identified five distinct subpopulations, including tamoxifen-sensitive and -resistant groups. Using a single-gene mathematical model, we discovered approximately 560-680 genes out of 6000 exhibiting multistable expression states in each subpopulation, including key estrogen-receptor-positive breast cancer cell survival genes, such as RPS6KB1 . A bifurcation analysis elucidated their regulatory mechanisms, and we mapped these genes into a molecular network associated with cell survival and metastasis-related pathways. Our modeling approach comprehensively identifies key regulatory genes for drug resistance acquisition, enhancing our understanding of potential drug targets in breast cancer., Competing Interests: The authors declare no conflicts of interest.

Here, we present a patient with hepatocellular carcinoma complicated by tumor thrombosis into the main portal trunk and perihepatic lymph node metastases who was treated with atezolizumab plus bevacizumab. Shrinkage of the main tumor, portal vein thrombosis, and lymph node metastases were achieved; therefore, hepatectomy with lymphadenectomy could be performed. Final pathology indicated a complete pathological response in the main tumor, portal vein thrombosis, and perihepatic lymph nodes. The patient is currently alive with no evidence of recurrence on radiological assessment at 3 months after surgery., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: In the EV-301 trial, enfortumab vedotin prolonged survival in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy and programmed cell death 1/programmed death-ligand 1 inhibitor. However, real-world Asian data are limited, and potential prognostic markers are non-existent. We aimed to investigate potential prognostic markers for enfortumab vedotin therapy in Asian patients., Methods: We retrospectively enrolled 61 Japanese patients treated with enfortumab vedotin therapy at our hospital and affiliated hospitals between January 2019 and September 2023., Results: Enrolled patients (38 men, 23 women; median age 74 [IQR: 68-79] years) had bladder cancer (26 patients) or upper-tract urothelial carcinoma (35 patients). Fifty-four patients reported adverse events (grade >3 in 12). Skin disorders, pruritus, and neuropathy were common adverse effects. The median overall survival was 17.1 months (95% confidence interval: 10.0-not applicable). In multivariate analysis, the C-reactive protein level was an independent marker predicting favorable overall survival with enfortumab vedotin. Patient characteristics did not differ between C-reactive protein-high and -low groups., Conclusions: Our study provides real-world data showing that enfortumab vedotin prolonged survival in Asian patients similar to the EV-301 trial. Additionally, the C-reactive protein level might be considered a prognostic marker of enfortumab vedotin therapy in such patients.

During aging, skin homeostasis is essential for maintaining appearance, as well as biological defense of the human body. In this study, we identified thrombospondin-1 (THBS1) and fibromodulin (FMOD) as positive and negative regulators, respectively, of the TGF-β1-SMAD4 axis in human skin aging, based on in vitro and in vivo omics analyses and mathematical modeling. Using transcriptomic and epigenetic analyses of senescent dermal fibroblasts, TGF-β1 was identified as the key upstream regulator. Bifurcation analysis revealed a binary high-/low-TGF-β1 switch, with THBS1 as the main controller. Computational simulation of the TGF-β1 signaling pathway indicated that THBS1 expression was sensitively regulated, whereas FMOD was regulated robustly. Results of sensitivity analysis and validation showed that inhibition of SMAD4 complex formation was a promising method to control THBS1 production and senescence. Therefore, this study demonstrated the potential of combining data-driven target discovery with mathematical approaches to determine the mechanisms underlying skin aging., Competing Interests: M.H. was an employee of Rohto Pharmaceutical Co. Ltd. at the time of submission of this article. This work was performed partially under an agreement between Osaka University and Rohto Pharmaceutical. A patent (JP 2022–047116) is associated with this study., (© 2024 The Author(s).)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a complication caused by antithyroid drugs, particularly propylthiouracil (PTU). Most patients experience organ failure due to the affects of the treatment regimen. We herein report the case of an 89-year-old woman whose severe AAV induced by PTU resulted in various instances of organ failure that eventually led to death after 9 years of PTU therapy. During autopsy, we identified five types of organ failure. As AAV is a potentially fatal disease, the development of various vasculitis symptoms during PTU therapy should therefore be carefully monitored.

Background: It remains controversial whether meniscal repair causes meniscal extrusion. This study aimed to investigate the effect of inside-out meniscal repair on meniscal dimensions in patients with meniscal tear of the mid-body-posterior horn., Methods: This retrospective study included 75 patients who underwent meniscal repair followed by MRI within 2 weeks after surgery between 2020 and 2022. Patients with a discoid lateral meniscus, pull-out repair, concomitant osteotomy, all-inside repair only, and revision surgery were excluded. Thirty-three meniscal tear treated using an inside-out arthroscopic repair technique were included in the lateral meniscus (LM, n = 19) and medial meniscus (MM, n = 14) tear groups. Thirty-six participants with intact meniscus were included as controls. Meniscal extrusion and posterior shift were measured on coronal and sagittal MRI pre-operatively and within 2 weeks postoperatively., Results: Preoperative coronal extrusion was significantly greater in the LM tear group than in the control group (P = 0.001). Coronal extrusion and posterior shift were significantly smaller postoperatively than preoperatively in the LM tear group (P < 0.001 and, P = 0.008, respectively). Pre- and postoperative coronal extrusion in the MM tear group were not significantly different (P = 0.291). Postoperative coronal extrusion in both LM and MM tear groups were not significantly correlated with the number of sutures required for repair (LM: P = 0.765, R = -0.076, MM: P = 0.1, R = 0.497)., Conclusions: The torn meniscus of the mid-body - posterior horn before surgery was extruded and shifted posteriorly in both LM and MM tears, and repair using an inside-out arthroscopic technique was effective in reducing meniscal extrusion and posteriors shift in the LM tear immediately after surgery., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

Purpose: To compare the clinical outcomes of anterior cruciate ligament (ACL) reconstruction between methods using quadriceps tendon with bone (QTB) and hamstring tendon (HT) in patients with hyperextension of the knee., Methods: The medical records of patients with knee hyperextension greater than 8° who underwent arthroscopic ACL reconstruction between October 2010 and October 2020 with follow-up for at least 2 years (median, 3 years; interquartile range [IQR], 2.0-4.6 years) were retrospectively reviewed. Side-to-side difference in anterior translation, pivot-shift test grade, Lysholm score, and graft intensity using the Howell grade on magnetic resonance imaging at final follow-up were compared between the QTB and HT groups., Results: The HT and QTB groups consisted of 42 patients and 21 patients, respectively. The overall mean age was 21.5 years (range, 14-48 years), and the median Tegner Activity Scale score was 6 (range, 3-9). Postoperatively, the median side-to-side difference in anterior translation was 1.75 mm (IQR, 1-3 mm) in the HT group and 1.0 mm (IQR, 0-1.75 mm) in the QTB group (P = .01). Pivot-shift testing showed grade 0 in 74.7%, grade 1 in 18.7%, and grade 2 in 6.6% of patients in the HT group and grade 0 in 85.7% and grade 1 in 14.3% of those in the QTB group (P = .03). The median postoperative Lysholm score was 99 in both groups. Graft signal intensity showed a significant between-group difference: grade I in 52%, grade II in 36%, and grade III in 12% of patients in the HT group versus grade I in 85.7%, grade II in 9.5%, and grade III in 4.8% of those in the QTB group (P = .03)., Conclusions: In patients who underwent ACL reconstruction for hyperextension of the knee, QTB yielded better clinical outcomes than HT with respect to anterior stability, rotational stability, and graft signal intensity on median 2-year follow-up magnetic resonance imaging., Level of Evidence: Level III, retrospective case-control study., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background/aim: The survival and prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who underwent surgical intervention after lenvatinib treatment is not well-understood., Patients and Methods: Seventy-six patients with advanced HCC who had lenvatinib treatment were retrospectively analyzed., Results: Of 70 patients who were treated with lenvatinib, 14 patients underwent surgical intervention after lenvatinib treatment for 4-28 weeks. Progression-free survival (PFS) was significantly longer in patients who underwent surgical intervention than in patients with non-surgical treatment (median, 8.6 vs. 5.1 months, p=0.019). Non-significantly longer overall survival (OS) was also observed in patients with surgical intervention compared to patients with non-surgical treatment (median, unreached vs. 21.0 months, p=0.206). In patients who underwent surgical intervention, two patients had a partial response, and 12 had stable disease according to RECIST ver. 1.1 criteria. The serum alpha-fetoprotein (AFP) level was significantly lower after lenvatinib treatment than before lenvatinib treatment (median, 19.2 vs. 196.5 ng/ml, p=0.0081). Eleven patients underwent curative surgery with a 14% major postoperative complication (Clavien-Dindo ≥IIIa) rate. Patients who exhibited decreases in AFP levels or maintained AFP levels within the normal range during lenvatinib treatment had significantly longer PFS (median, 8.6 vs. 3.0 months, p=0.0009) and OS (median, unreached vs. 12.4 months, p=0.012) compared to those with persistently elevated AFP levels beyond the normal range., Conclusion: Surgical intervention after lenvatinib treatment for advanced HCC was associated with longer PFS. Patients exhibiting decreased AFP levels or maintaining AFP levels within the normal limit may be suitable candidates for surgical intervention after lenvatinib treatment for advanced HCC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The process and molecular mechanisms underlying the formation and destruction of a pseudo-capsule (PC) in clear cell renal cell carcinoma (ccRCC) are poorly understood. In the present study, the PCs of surgical specimens from primary tumors and metastatic lesions in 169 patients with ccRCC, and carcinogen-induced ccRCC rat models were semi-quantified using the invasion of PC (i-Cap) score system. This was based on the relationship among the tumor, PC and adjacent normal tissue (NT) as follows: i-Cap 0, tumor has no PC and does not invade NT; i-Cap 1, tumor has a complete PC and does not invade into the PC; i-Cap 2, tumor with focal absences in the PC, which partially invades the PC but not completely through the PC; i-Cap 3, tumor crosses the PC and invades the NT; i-Cap 4, tumor directly invades the NT without a PC. The study suggested that PC formation was not observed without physical compression, and also revealed that tumor invasion into the PC was a prognostic factor for postoperative oncological outcomes. Higher i-Cap, Fuhrman grade and tumor size were independent poor prognostic factors for postoperative disease-free survival. mRNA expression arrays generated from carcinogen-induced ccRCC rat models were used to explore genes potentially associated with the formation and destruction of a PC. Subsequently, human ccRCC specimens were validated for four genes identified via expression array; the results revealed that collagen type 4A2, matrix metalloproteinase-7 and l-selectin were upregulated alongside the progression of i-Cap score. Conversely, endoglin was downregulated. In conclusion, the present study provides insights into the formation and destruction of a PC, and the results may aid the treatment and management of patients with ccRCC., Competing Interests: All authors confirm that they have no competing interests., (Copyright: © 2024 Shimizu et al.)

Purpose: The International Bladder Cancer Group designated the subgroup that is resistant to Bacillus Calmette-Guérin (BCG) but does not meet the criteria for BCG-unresponsive NMIBC as "BCG-exposed high-risk NMIBC" to guide optimal trial design. We aimed to investigate the treatment patterns and prognoses of patients with BCG-exposed NMIBC., Methods: We conducted a retrospective chart review of 3283 patients who received intravesical BCG therapy for NMIBC at 14 participating institutions between January 2000 and December 2019. Patients meeting the criteria for BCG-exposed and BCG-unresponsive NMIBC, as defined by the Food and Drug Administration and International Bladder Cancer Group, were selected. To compare treatment patterns and outcomes, high-risk recurrence occurring more than 24 months after the last dose of BCG was defined as "BCG-treated NMIBC." In addition, we compared prognoses between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC., Results: Of 3283 patients, 108 (3.3%), 150 (4.6%), and 391 (11.9%) were classified as having BCG-exposed, unresponsive, and treated NMIBC, respectively. BCG-exposed NMIBC demonstrated intermediate survival curves for intravesical recurrence-free and progression-free survival, falling between those of BCG-unresponsive and treated NMIBC. Among patients with BCG-exposed NMIBC, 48 (44.4%) received BCG rechallenge, which was the most commonly performed treatment, and 19 (17.6%) underwent early cystectomy. No significant differences were observed between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC., Conclusions: The newly proposed definition of BCG-exposed NMIBC may serve as a valuable disease subgroup for distinguishing significant gray areas, except in cases of BCG-unresponsive NMIBC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

BACKGROUND Pseudo-Brown syndrome is characterized by dysfunction of the superior oblique tendon-trochlear complex. Canine tooth syndrome, which involves superior oblique palsy with pseudo-Brown syndrome, results from damage to the trochlear and superior oblique tendon from dog bites around the eye. This report describes a variant of canine tooth syndrome without pseudo-Brown syndrome following a dog bite around the left upper eyelid. In this case, magnetic resonance imaging (MRI) facilitated early diagnosis and therapeutic intervention. CASE REPORT A 19-year-old man presented with torsional diplopia following a dog bite around the left upper eyelid and forehead. Five days after the injury, an alternate prism cover test revealed 6 prism diopters (Δ) exotropia and 5Δ left hypertropia. Ocular motility showed no significant limitation in elevation or depression during adduction. MRI performed on the same day showed a high-signal area extending from the superior oblique tendon to the trochlear region and the superior oblique muscle belly of the left eye. A diagnosis of canine tooth syndrome without pseudo-Brown syndrome was made and oral steroids were administered. Ocular alignment did not improve, so left inferior oblique myotomy was performed 7 months after the injury. The patient's cyclovertical diplopia resolved postoperatively. CONCLUSIONS Dog bites around the eye can result in abnormalities of the extraocular muscles. Early MRI may be useful for diagnosis and determining treatment strategies. This report has highlighted the importance of rapid assessment and management of patients with dog bites involving the eye.

In patients with intractable epilepsy, seizure focus resection can yield favorable seizure outcomes. First, the localization of the seizure focus is estimated by noninvasive methods such as magnetic resonance imaging(MRI), video-electroencephalography(EEG)monitoring, nuclear medicine examinations, magnetoencephalography, and neuropsychological tests. A subgroup of patients may require additional information obtained from the intracranial EEG. There are two major methods for intracranial EEG: intracranial EEG with subdural grid electrodes(SDG)and stereotactic electroencephalography. If the estimated seizure focus overlaps with the eloquent area in noninvasive studies, the margin and extent of the resection are determined by the results of intracranial EEG and functional mapping by electrical cortical stimulation. Herein, we present a case of lobe epilepsy with subtle MRI lesions in the superior temporal sulcus of the language-dominant hemisphere. The results of the SDG and functional mapping showed that the seizure onset zone overlapped with the language area. Resection of the middle and inferior temporal gyri and multiple transections of the language area resulted in Engel IIB seizure outcomes. In such cases, a thorough preoperative simulation is required to determine the best resection margin for seizure control and functional preservation.

Materials that intrinsically exhibit localized surface plasmon resonance (LSPR) in the visible region have been predominantly researched on nanoparticles (NPs) composed of coinage metals, namely Au, Ag, and Cu. Here, as a coinage metal-free intermetallic NPs, colloidal PtIn 2 NPs with a C1 (CaF 2 -type) crystal structure are synthesized by the liquid phase method, which evidently exhibit LSPR at wavelengths similar to face-centered cubic (fcc)-Au NPs. Computational simulations pointed out differences in the electronic structure and photo-excited electron dynamics between C1-PtIn 2 and fcc-Au NPs; reduces interband transition and stronger screening with smaller number of bound d-electrons compare with fcc-Au are unique origins of the visible plasmonic nature of C1-PtIn 2 NPs. These results strongly indicate that the intermetallic NPs are expected to address the development of alternative plasmonic materials by tuning their crystal structure and composition., (© 2024 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Small-cell neuroendocrine carcinoma (SCNEC) of the cervix is a rare disease characterized by a high incidence of mixed tumors with other types of cancer. The mechanism underlying this mixed phenotype is not well understood. This study established a panel of organoid lines from patients with SCNEC of the cervix and ultimately focused on one line, which retained a mixed tumor phenotype, both in vitro and in vivo. Histologically, both organoids and xenograft tumors showed distinct differentiation into either SCNEC or adenocarcinoma in some regions and ambiguous differentiation in others. Tracking single cells indicated the existence of cells with bipotential differentiation toward SCNEC and adenocarcinomas. Single-cell transcriptional analysis identified three distinct clusters: SCNEC-like, adenocarcinoma-like, and a cluster lacking specific differentiation markers. The expression of neuroendocrine markers was enriched in the SCNEC-like cluster but not exclusively. Human papillomavirus 18 E6 was enriched in the SCNEC-like cluster, which showed higher proliferation and lower levels of the p53 pathway. After treatment with anticancer drugs, the expression of adenocarcinoma markers increased, whereas that of SCNEC decreased. Using a reporter system for keratin 19 expression, changes in the differentiation of each cell were shown to be associated with the shift in differentiation induced by drug treatment. These data suggest that mixed SCNEC/cervical tumors have a clonal origin and are characterized by an ambiguous and flexible differentiation state., Competing Interests: Disclosure Statement J.K., K.O., and M.I. are members of the Department of Clinical Bio-resource Research and Development at Kyoto University, which is sponsored by KBBM, Inc. H.U. is an employee of KBBM, Inc., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: The burden of epilepsy is thought to be high but is difficult to measure. Very few studies in Japan have attempted to estimate prevalence and incidence rates of epilepsy in Japan., Methods: This retrospective cohort study used commercially collected nationwide insurance claims data from a cohort of 10 million persons between 2012 and 2019 among those aged 0 to 74 years. Using the claims data, cases were identified, and incidence and prevalence rates were estimated., Results: A total of 9,864,278 persons were included. The average age was 34.5 (standard deviation, 18.5) years. A total of 77,312 persons were diagnosed with epilepsy over the 8-year observation period, with a prevalence rate of 6.0 per 1,000 persons with almost no difference by gender. The highest rates were seen among those aged 70-74 years; prevalence rates tended to rise with calendar year (5.4/1,000 in 2012 and 6.0/1,000 in 2019). The incidence rate of epilepsy was 72.1 per 100,000 person-years with slightly higher rates seen among females. Incidence rates were highest at ages less than 12 months (199.8/100,000 person-years), followed by the eldest age group (70-74 years, 179.4/100,000 person-years)., Conclusion: Understanding the magnitude of disease burden is the basis of determining health policies. In this study, the prevalence and incidence of epilepsy in Japan was shown based on the analysis results of a large-scale general population insurance claims data covering all over Japan.

Introduction: This study aimed to evaluate the meniscal size of asymptomatic discoid lateral meniscus (DLM) and compare it with that of normal lateral meniscus (LM) and to compare changes in meniscal dimensions with age among patients with asymptomatic DLM and those with normal LM using magnetic resonance imaging (MRI)., Materials and Methods: We retrospectively reviewed the medical records, including MRI data, of patients with asymptomatic DLM (DLM group) or normal LM (control group). Width and extrusion of both DLM and normal LM and tibial length were measured and compared using mid-coronal and mid-sagittal MR images. Meniscal size and sagittal and coronal meniscal ratio according to age, as well as differences between DLM and normal menisci, were also evaluated., Results: Thirty-four knees were included in the DLM group, whereas the control group comprised of 50 patients. The DLM group showed significantly less meniscal extrusion, greater coronal width, posterior capsule distance, sagittal meniscal length, and sagittal meniscal ratio than the control group (DLM: 0.1 ± 0.3 mm, 23.3 ± 2.2 mm, 5.4 ± 2.4 mm, 25.1 ± 2.8 mm, 61 ± 6%, and control: 0.4 ± 0.4 mm, 9.5 ± 2.3 mm, 2.5 ± 1.2 mm, 30.2 ± 2.6 mm, 71 ± 4%, respectively). The coronal meniscal ratio decreased with age in both the control (p = 0.001) and DLM (p = 0.037) groups. The sagittal meniscal ratio (p = 0.001) and minimum height (p = 0.04) decreased and the anterior capsule distance (p = 0.035), posterior capsule distance (p = 0.026), and entire sagittal length (p = 0.005) increased with age in the DLM group, while the distance between the meniscal inner margins (p = 0.019) increased with age in the control group., Conclusions: The meniscal ratio in the sagittal plane of the DLM group was significantly lower than that of the control group. The sagittal meniscal ratio of asymptomatic DLM decreased with age, indicating that the size of asymptomatic DLM does not change with age., Level of Evidence: III: Retrospective comparative study., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Ankle-foot-complex mobility impairments, which can be assessed by the difference between the sitting and standing positions, are related to an increase in the load on the knee and hip joints during the stance phase of the gait., Research Question: What is the relationship between the ankle-foot-complex mobility during static weight bearing and the mechanical stresses on the knee and hip joints throughout the stance phase?, Methods: Ankle-foot-complex mobility and gait data were collected from 26 healthy adults. The complex mobility was established by comparing the foot indices, measured using a three-dimensional foot scanner, in sitting and standing positions. The gait data were acquired using eight cameras (recording at 100 Hz) and three force plates (recording at 1000 Hz). Stance phase data were collected via ground reaction forces. The stance phase was dissected into shock absorption and propulsion phases, during which the external knee and hip adduction moment impulses (KAMi, HAMi) were recorded. The correlation between the ankle-foot-complex mobility during static weight bearing and KAMi and HAMi during the stance phase was examined using Pearson's product-moment correlation coefficients., Results: This study revealed that KAMi correlated with medial malleolus mobility (r = -0.44) throughout the stance phase. Furthermore, in the propulsive phase, KAMi correlated with calcaneus (r = 0.51) and navicular (r = -0.50) mobilities, whereas HAMi correlated with calcaneus mobility (r = -0.40)., Significance: The study provides insights into the relationship between the static mobility of the ankle-foot complex in healthy individuals and mechanical stress during the stance phase. Calcaneus and navicular mobilities were related to efficient push-off in the propulsive phase. Medial malleolus mobility was related to the control of the lateral tilt of the lower limb and ankle dorsiflexion motion throughout the stance phase., Competing Interests: Declaration of Competing Interest There are no conflicts of interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)