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Naotatsu Otsuji,1 Kumiya Sugiyama,1,2 Takayoshi Owada,1 Hajime Arifuku,1 Kenya Koyama,1 Hirokuni Hirata,1 Yasutsugu Fukushima1 1Department of Respiratory Medicine and Clinical Immunology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan; 2National Hospital Organization Utsunomiya Hospital, Utsunomiya, Tochigi, JapanCorrespondence: Kumiya Sugiyama, National Hospital Organization Utsunomiya Hospital, 2160, Shimo-Okamoto, Utsunomiya, Tochigi, 329-1193, Japan, Email sugiyama@dokkyomed.ac.jpPurpose: The prognosis of rheumatoid arthritis (RA) with interstitial lung disease (ILD) is particularly poor. Although drugs that do not contribute to the progression of ILD should be used in RA treatment, none have been established. This study evaluated the safety of tocilizumab in terms of ILD activity.Patients and Methods: This study prospectively enrolled all 55 patients with RA complicated by ILD who were treated with tocilizumab at Dokkyo Medical University Saitama Medical Center from April 2014 to June 2022. The outcome measures were MMP-3 and KL-6 as biomarkers of RA and ILD activity, respectively, and the relationship between them was analyzed.Results: Both MMP-3 and KL-6 were significantly improved at 6 months of treatment (P < 0.001 and P < 0.05, respectively), and a weak correlation between MMP-3 and KL-6 was observed (R2 = 0.086, P = 0.087). The group with increased MMP-3 due to RA progression had significantly higher KL-6 at 6 months compared with the group with RA improvement (P < 0.05). Also, the group with ILD progression on computed tomography had significantly higher MMP-3 compared with the groups with improvement or no change of ILD (P < 0.05 and P < 0.01, respectively). The mortality rate was 0% at 6 months, 2.0% at 1 year, 16.7% at 2 years, and 32.4% at 3 years, and mortality from acute exacerbation of ILD due to respiratory infection increased over time.Conclusion: RA activity and ILD activity were found to be related at 6 months of treatment. Tocilizumab does not seem to affect the mechanism of ILD progression, as most patients showed improvement in both MMP-3 and KL-6 with tocilizumab within 6 months, when this drug would be expected to affect the lungs directly. However, respiratory infection exacerbated ILD from 1 year after the start of treatment. As immunosuppressive drugs, including tocilizumab, have a risk of respiratory infection, it is important to identify early signs of infection.Keywords: interstitial lung disease, Krebs von den Lungen-6, KL-6, matrix metalloproteinase-3, MMP-3, rheumatoid arthritis, mortality, tocilizumab

The topological and chemical short-range ordering (TSRO and CSRO) of Pd82Ge18 amorphous alloys prepared by the single-roll liquid quench method were analyzed using a combination of anomalous X-ray scattering and reverse Monte Carlo (RMC) simulation. The degree of development of TSRO and CSRO in the amorphous structure model made with the RMC simulation (RMC model) was evaluated by comparison with the dense random packing model (DRP model) calculated using metallic and covalent atomic radii. In the RMC model, a shortening of the Pd--Ge nearest neighbor correlation and a decrease in the coordination number around Ge were observed. Voronoi polyhedral analysis was performed to evaluate the local geometrical structure around the Pd and Ge atoms. Although the DRP structure can reasonably approximate the local structure around the Pd atoms, the TTP structure corresponding to the local structure in crystalline Pd2Ge develops around the Ge atoms as a characteristic TSRO. However, the preferential coordination of Pd atoms around Ge, which is a CSRO associated with the TTP structure in the crystalline phase, was not observed. These results indicate that strong CSRO does not necessarily accompany the TTP structures in metal-semimetal amorphous alloys. [ABSTRACT FROM AUTHOR]

Background: A subset of patients with traumatic cardiac arrest is salvageable when the reversible causes of cardiac arrest are promptly treated. However, prognosis and risk factors of survivors upon hospital admission after traumatic cardiac arrest remain unclear. We aimed to describe the outcomes, identify risk factors, and develop a simple risk-scoring model for patients resuscitated from traumatic cardiac arrest., Methods: This observational multicenter study analyzed data from the Japan Trauma Data Bank from January 1, 2019, to December 31, 2021. Patients who underwent cardiopulmonary resuscitation in the emergency department and survived to the day after hospital admission for traumatic cardiac arrest were included. Factors associated with survival to hospital discharge were determined using mixed-effects multivariable logistic regression analysis. A simple scoring model was developed to stratify the probability of survival to hospital discharge., Results: In total, 452 patients from 119 hospitals (median age, 64 years; 334 [74.4%] men) were included in the analysis. Of these, 130 (28.8%) survived until discharge. Penetrating injury, signs of life upon hospital arrival, and Injury Severity Score were significantly associated with survival at hospital discharge. A scoring model that assigned 1 point each for penetrating injury and signs of life upon hospital arrival effectively stratified the probability of survival to hospital discharge, with scores of 0, 1, and 2 corresponding to survival probabilities of 12.2%, 35.2%, and 83.3%, respectively., Conclusion: This study described the outcomes and risk factors of patients resuscitated from traumatic cardiac arrest. Our simple scoring model effectively stratified the likelihood of survival to hospital discharge., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Atomoxetine, a selective norepinephrine reuptake inhibitor for attention-deficit hyperactivity disorder, may lead to severe complications, notably cardiac issues, upon overdose. We present a unique case of venoarterial extracorporeal membrane oxygenation (VA-ECMO) rescue for atomoxetine-induced cardiogenic shock., Case Presentation: We report a 30-year-old man who, after ingesting a significant overdose of atomoxetine, experienced seizures and severe cardiogenic shock, necessitating VA-ECMO for resuscitation. While prior reports have noted cardiovascular complications like QTc prolongation and Takotsubo cardiomyopathy following atomoxetine overdose, this case is notable for its life-threatening circulatory failure, which required ECMO intervention. Swift recognition coupled with VA-ECMO initiation, endoscopic medication removal, intravenous lipid emulsion, and activated charcoal may have played a pivotal role in stabilizing the patient and facilitating recovery., Conclusion: Healthcare practitioners should recognize the severe cardiac complications of atomoxetine overdose. Careful monitoring with ECG and echocardiography, along with providing intensive care, is crucial in managing critical cases., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Aim: The requirement during the COVID-19 pandemic to provide extracorporeal membrane oxygenation (ECMO) treatment regardless of experience caused high levels of anxiety among healthcare professionals. The aim of the present study was to evaluate the effectiveness of an in situ interprofessional simulation training conducted to improve readiness and preparedness for ECMO management of patients with COVID-19 at a non-high-volume ECMO centre., Methods: Three emergency physicians, three clinical engineers and two nurses attended the 3-h simulation held at Hirosaki University Hospital in December 2021, during the COVID-19 pandemic. The training comprised a 30-min briefing, a 1-h ECMO circuit change session, a 1-h in-hospital transfer simulation for CT and a 30-min debriefing. Before and after the training, participants completed an online survey of their emotions, based on the Japanese version of the Medical Emotion Scale (J-MES). Related-samples Wilcoxon signed rank test was used to assess potential changes in emotional responses before and after the simulation, and p  < 0.05 was considered to indicate significance., Results: Participants' positive deactivating emotions increased from a median of 3.3 (range, 2.0-4.5) before the simulation to 4.0 (range, 2.5-5.0) after the simulation ( p  = 0.02), which indicates favourable performance according to the control value theory of educational psychology. There was no statistically significant change in other emotional categories., Conclusion: Participants' positive deactivating emotions increased significantly following an in situ ECMO simulation training, which indicates the efficacy of the training for improving the quality of ECMO management in patients with COVID-19., Competing Interests: The authors declare no conflicts of interest for this article., (© 2024 The Author(s). Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Introduction: Language that assumes gender and sex are binary and aligned is pervasive in medicine and is often used when teaching on physiology and pathology. Information presented through this lens oversimplifies disease mechanisms and poorly addresses the health of gender and sexually diverse (GSD) individuals. We developed a training session to help faculty reference gender and sex in a manner that would be accurate and inclusive of GSD health., Methods: The 1-hour session for undergraduate and graduate medical educators highlighted cisgender and binary biases in medical teachings and introduced a getting-to-the-root mindset that prioritized teaching the processes underlying differences in disease profiles among gender and sex subpopulations. The training consisted of 30 minutes of didactic teaching and 20 minutes of small-group discussion. Medical education faculty attended and self-reported knowledge and awareness before and after the training. Results were compared using paired t tests. Expenses included fees for consultation and catering., Results: Forty faculty participated (pretraining survey n = 36, posttraining survey n = 21). After the training, there was a significant increase in self-reported awareness of the difference between gender and sex ( p = .002), perceived relevance of gender to teachings ( p = .04), and readiness to discuss physiological drivers of sex-linked disease ( p = .005)., Discussion: Participants reported increased understanding and consideration of gender and sex in medical education; feedback emphasized a desire for continued guidance. This easily adaptable session can provide an introduction to a series of medical teachings on gender and sex., (© 2024 Crosby et al.)

Background and Objectives: In magnetic resonance-guided focused ultrasound (MRgFUS) procedures, headache is a frequent symptom and cause of treatment discontinuation. Herein, we assessed the efficacy of scalp nerve block (SNB) for alleviating headache during MRgFUS procedures., Methods: The effect of SNB on intraprocedural headache was examined by retrospectively comparing 2 patient cohorts at a single institution. During the study period from April 2020 to February 2022, an SNB protocol for all patients with a skull density ratio ≤0.55 was instituted on October 6, 2021. The number of patients with a skull density ratio ≤0.55 was 34 before the protocol and 36 afterward. Headache intensity was evaluated using a numerical rating scale (NRS) after each sonication. To evaluate the effect of SNB on headache intensity, multiple regression analysis was performed per patient and per sonication. In the per-patient analysis, the effect of SNB was evaluated using the maximum NRS, mean NRS, and NRS at the first ultrasound exposure that reached 52.5°C. In the per-sonication analysis, the effect of SNB was evaluated not only for the entire sonication but also for sonications classified into ≤9999 J, 10 000 to 29 999 J, and ≥30 000 J energy doses., Results: With SNB, headache alleviation was observed in the NRS after the first sonication that reached 52.5°C in each patient (β = -2.40, 95% CI -4.05 to -0.758, P = .00499), in the NRS when all sonications were evaluated (β = -0.647, 95% CI -1.19 to -0.106, P = .0201), and in the NRS when all sonications were classified into 10 000 to 29 999 J (β = -1.83, 95% CI -3.17 to -0.485, P = .00889)., Conclusion: SNB significantly reduced headache intensity during MRgFUS, especially that caused by sonication with a moderate-energy dose. These findings suggest that scalp nerves play a role in headache mechanisms during MRgFUS., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Delirium is a distressing condition in terminally ill cancer patients, often treated with antipsychotics. Administering them orally, subcutaneously, or intravenously can be challenging in severely agitated patients. Transdermal antipsychotic patches offer an alternative, but their use for terminal delirium remains underexplored. We present the case of a 73-year-old man with advanced diffuse large B cell lymphoma who developed severe mixed delirium during third-line chemotherapy. Nonpharmacological interventions and oral risperidone plus intravenous haloperidol failed to improve his condition. Subsequently, a transdermal blonanserin patch was applied, resulting in the resolution of hallucinations on day 1 and agitation on day 3, allowing improved communication. The patch was easily applied daily without notable adverse events. However, he deteriorated a week later with an estimated survival of days, ultimately requiring continuous midazolam for refractory agitation. This case underscores the potential of transdermal blonanserin patches for delirium in terminally ill cancer patients, emphasizing the need for future prospective studies.

Specific Hawaiian fruit flies have an extra crossvein (ECV) in the wing vein network which connects contiguously with another crossvein and forms a unique cruciform topology. These flies are distinguished by their large wings and their allometrically small vein diameters compared to those of typical fruit flies. Small vein diameters may increase frictional energy loss during internal blood transport, although they lead to an improvement in the wing's moment of inertia. Our hypothesis was that the ECV's presence would reduce the hydraulic resistance of the entire vein network. To investigate the hemodynamic effects of its presence, the flow rate of blood and frictional pressure loss within the vein networks was simulated by modeling them as hydraulic circuits. The results showed a 3.1% reduction in pressure loss owing to the network topology created by the presence of the ECV. This vein and its contiguous crossvein diverted part of the blood from the wing veins topologically parallel to them, reducing the pressure loss in these bypassed veins. The contiguity of the ECV to the other crossvein provided the shortest blood transfer route and lowest pressure drop between these crossveins. The results suggest that the presence of the ECV may counterbalance the heightened resistance caused by constricted veins.

Valproic acid is commonly used for treating seizures and psychiatric disorders. Valproic acid is a common anticonvulsant drug causing overdose for suicidal purposes. The most common symptom of valproic acid poisoning is central nervous system damage. Most cases result in mild to moderate drowsiness, while in severe cases, fatal cerebral edema and coma have been reported. Other complications include respiratory depression, hepatotoxicity, thrombocytopenia, and multi-organ failure resulting in circulatory collapse. Herein, we present a case of a 42-year-old woman who ingested an overdose of 600 mg nitrazepam, 50 mg olanzapine, and 35,600 mg valproic acid. The maximum daily doses for nitrazepam, olanzapine, and valproic acid are 15, 20, and 1200 mg, respectively. This overdose led to reversible arginine vasopressin (AVP) deficiency as a rare but significant complication. The deficiency led to polyuria with dilute urine, which was effectively suppressed by AVP administration. This case highlights the potential for reversible AVP deficiency as a rare but significant complication of valproic acid overdose. Early diagnosis and appropriate management are crucial for favorable outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. 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, Kato et al.)

Nitroxyl radical compounds, such as 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), are stable radical compounds with a variety of unique characteristics, including fluorescence quenching. In this study, we investigated the fluorescence quenching effect of nortropine N-oxyl (NNO), which is a highly active nitroxyl radical that is more active than TEMPO in oxidation catalysis. The fluorescence intensity of 7-amino-4-methylcoumarin (AMC) was quenched by NNO and TEMPO to 5% and 95% of the initial fluorescence intensity, respectively, indicating highly efficient quenching by NNO. In addition, we used this reaction to measure glutathione concentration. The quenching effect of NNO was abrogated by the chemical reaction with glutathione, resulting in restoration of AMC fluorescence. This response was observed at glutathione concentrations from 10 µM to 1 mM, and good calibration curves were obtained from 10 to 250 µM., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We fabricated porous particles incorporating sugars (mannitol, sucrose, or dextran) and fenofibrate nanoparticles (FNPs) by using spray-freeze-drying (SFD). The type of sugar significantly influenced the pore architecture of the resulting SFD particles. Rapid freezing of droplets containing dextran produced ice encapsulation within a dextran matrix, forming porous dextran particles. In the presence of FNPs, the particle size (approximately 4 μm) and pore volume (0.3 cm 3 /g) of SFD dextran were barely affected. In contrast, SFD particles derived from mannitol and sucrose exhibited denser structures with a lower pore volume than dextran. SFD mannitol incorporating FNPs produced porous structures. FNPs containing surfactant and polymer, which reduced surface tension and increased viscosity, promoted the formation of small droplets with a polymeric structure and porous particles with a relatively sharp size distribution with a median around 5 μm. FNPs were uniformly distributed in SFD dextran, which featured large pore structures, whereas in SFD mannitol, the Raman signal of FNPs was more broadly distributed across the powder samples. Both morphologies contributed to enhancing the FNP dispersibility within a redispersed suspension of SFD particles. FNPs in SFD mannitol and dextran matrices maintained their particle size distribution from before SFD, showing no aggregation upon redispersion. Dextran formed a highly porous network irrespective of the presence of FNPs, whereas mannitol tended to alter the particle attributes upon FNP inclusion. In conclusion, SFD particles derived from dextran and mannitol might help to increase FNP dispersibility by increasing the formation of porous architectures.

Background: Gentamicin is a commonly used antibiotic with synergistic effects that is administered once or multiple times daily. However, the influence of the daily administration frequency on renal function has not yet been identified. This study aimed to investigate the effect of the daily dosing frequency on worsening renal function in patients receiving gentamicin., Methods: This study included 35 patients undergoing gentamicin treatment who had at least one serum trough level measured and underwent therapeutic drug monitoring (TDM). We evaluated the influence of daily dosing frequency on gentamicin trough concentration and the risk of acute kidney injury (AKI)., Results: Compared to patients who received gentamicin once-daily dosing (n = 22), patients who received multiple-daily dosing (n = 13) had significantly higher initial and minimum trough concentrations after TDM. The proportion of patients with trough concentrations lower than 1.0 µg/mL was significantly higher in the once-daily dosing group at the initial trough concentration, whereas there was no significant difference at the minimum trough concentration after TDM. AKI developed in nine patients; however, there was no significant difference in the incidence of AKI according to the frequency of daily gentamicin dosing. In contrast, a higher minimum trough concentration after TDM was found to be a risk factor for AKI development with an odds ratio of 9.2 (95% confidence intervals; 1.3-65.5)., Conclusion: A higher trough concentration of gentamicin correlated with a higher incidence of AKI. The risk of developing AKI may be reduced by choosing a once-daily dosing regimen or implementing TDM., (© 2024. The Author(s).)

Objective: Tixagevimab/cilgavimab is a cocktail of two long-acting monoclonal antibodies approved for pre-exposure prophylaxis (PrEP) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (cause of coronavirus disease 2019 [COVID-19]) in immunocompromised (IC) or high-risk patients. We investigated the patient characteristics and clinical outcomes of IC patients administered tixagevimab/cilgavimab for PrEP in real-world use in Japan., Methods: This observational study used anonymous secondary data from Real-World Data Co., Ltd. for IC patients aged ≥12 years administered tixagevimab/cilgavimab between September 2022 and September 2023. We analyzed the baseline characteristics and event-rates of COVID-19-related clinical outcomes within 6 months of administration., Results: Data were analyzed for 397 IC patients. About half (53.4 %) were male and the median age was 71.0 (interquartile range 61.0, 77.0) years. Malignancy (97.2 %), cardiovascular disease (71.3 %), and diabetes (66.5 %) were frequent comorbidities. Systemic corticosteroids and immunosuppressants were prescribed to 87.4 % and 24.9 %, respectively. The two most common target clinical conditions were active therapy for hematologic malignancies (88.2 %) and treatment with B cell-depleting therapies (57.4 %). The event-rates per 100 person-months (95 % confidence interval; number) for medically attended COVID-19, COVID-19 hospitalization, in-hospital mortality due to COVID-19, and all-cause death were 4.14 (3.06-5.48; n = 49), 1.74 (1.09-2.64; n = 22), 0.07 (0.00-0.42; n = 1), and 0.60 (0.26-1.17; n = 8), respectively., Conclusion: This is the first report using a multicenter database to describe the clinical characteristics and COVID-19-related outcomes of IC patients administered with tixagevimab/cilgavimab in real-world settings in Japan. This cohort of IC patients who received tixagevimab/cilgavimab included many elderly patients with comorbidities., Competing Interests: Declaration of competing interest Toshibumi Taniguchi has received lecture fees from AstraZeneca K.K. Tomoyuki Homma, Yoichi Tamai, Yoshifumi Arita, Masakazu Fujiwara, Naho Kuroishi, Keiji Sugiyama, Shinichi Kanazu and Atsushi Maruyama are employees of AstraZeneca K.K., (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.)

Aim: Patients with the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) are unstable and often experience rearrest, after which ROSC may be reattained. This study investigated the incidence and risk factors of post-ROSC events (rearrest and subsequent reattainment of ROSC) and their impact on outcomes in patients with prehospital ROSC following OHCA., Methods: Patients with OHCA and prehospital ROSC were identified from the Tokyo Fire Department database between 1 January 2018 and 31 December 2022. The factors associated with post-ROSC events and their impact on 1-month favourable neurological outcome (cerebral performance category scale: 1 or 2) were assessed using multivariable logistic regression analysis., Results: Overall, 64,000 individuals experienced OHCA, and 6,190 (9.7%) had ROSC. Rearrest was confirmed in 28.4% of patients with ROSC, and was associated with age, time of emergency call, location of cardiac arrest, dispatcher instruction regarding cardiopulmonary resuscitation, first recorded cardiac rhythm, bystander cardiopulmonary resuscitation, defibrillation by a bystander, response time, and prehospital interventions. ROSC reattainment was confirmed in 34.5% of patients with rearrest and associated with the first recorded cardiac rhythm and defibrillation by a bystander. Patients without rearrests had the highest proportion of favourable neurological outcomes, followed by those with solved and unsolved rearrests (38.6% vs. 22.4% and 4.4%, P < 0.001). The difference remained significant after adjustment for confounders., Conclusion: This study revealed population-based incidence and risk factors of post-ROSC events. Rearrest was common, leading to unfavourable neurological outcome; however, its deleterious impact may be mitigated by successful resuscitation efforts., 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.)

An asymptomatic 75-year-old man who underwent transverse colon cancer surgery two years previously presented with retroperitoneal fibrosis (RPF) around the ventral sacral and right external iliac artery and vein on abdominal computed tomography (CT) during a routine surveillance visit. We assumed cancer recurrence or immunoglobulin G4 (IgG4)-related disease (RD), but although generic tumor markers and IgG4 levels were normal, soluble interleukin 2 receptor (sIL-2R) was elevated at 569 U/mL (reference: 122-496 U/mL). No diagnosis was made at this time, and the patient was followed up. He subsequently developed edema of both lower extremities. Abdominal enhanced CT showed an enlarged RPF without invasion of surrounding organs and with a delayed contrast effect, and positron emission tomography-CT showed fluorodeoxyglucose accumulation in the same area but a lower standardized uptake value (SUV) than at the time of transverse colon cancer diagnosis. Although generic tumor markers and IgG4 levels remained within the reference range, sIL-2R was further elevated to 1100 U/mL. An open biopsy and histopathology showed a high IgG4/IgG-positive cell ratio and infiltration of IgG4-positive plasma cells. The patient was finally diagnosed with IgG4-RD RPF. In cases of RPF after colorectal cancer surgery, the combined findings of elevated sIL-2R, lack of infiltration into surrounding organs, and lower SUV values ​​than at the cancer site could provide useful information to aid the diagnosis of IgG4-RD RPF., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. 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, Kakehi et al.)

Undifferentiated sarcoma of the liver is rare, especially in adults, and is an aggressive malignancy that originates from the primary mesenchymal tissues. A 53-year-old man was referred to our hospital for further evaluation of a low-grade fever. Contrast-enhanced CT revealed an 18-cm tumor in the right lobe of the liver. The tumor was characterized by low-density areas suspected of cystic components, a high-density area suspected of hemorrhage, and contrast enhancement in the thickened marginal and internal septa. MRI revealed a high-intensity tumor with a heterogeneous structure on T2-weighted images. Angiosarcoma of the liver with intratumoral hemorrhage was suspected, and right hepatectomy was performed. The pathological diagnosis was an undifferentiated sarcoma based on the presence of undifferentiated mesenchymal tumor cells with a stellate to spindle-shaped pleomorphism. Following a multidisciplinary discussion, 4 courses of the AI regimen (doxorubicin and ifosfamide)were administered as adjuvant chemotherapy, and no recurrence was confirmed at 2 years and 6 months follow-up. Our case suggests that radical resection followed by adjuvant chemotherapy may contribute to a favorable prognosis for undifferentiated sarcoma of the liver.

Objective:  Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture force of the murine aorta, thereby explaining the outcomes of clinical studies and assessing the added value of approved drugs in vascular Ehlers-Danlos syndrome (vEDS). Here, we applied our approach to six additional mouse hAD models., Material and Methods:  We used two mouse models ( Fbn1C1041G and Fbn1mgR ) of Marfan syndrome (MFS) as well as one smooth-muscle-cell-specific knockout (SMKO) of Efemp2 and three CRISPR/Cas9-engineered knock-in models ( Ltbp1 , Mfap4 , and Timp1 ). One of the two MFS models was subjected to 4-week-long losartan treatment. Per mouse, three rings of the thoracic aorta were prepared, mounted on a tissue puller, and uniaxially stretched until rupture., Results:  The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS. In contrast, the Ltbp1 , Mfap4 , and Timp1 knock-in models presented no impaired aortic integrity. As expected, losartan treatment reduced aneurysm formation but surprisingly had no impact on the aortic rupture force of our MFS mice., Conclusion:  Our read-out system can characterize the aortic biomechanical integrity of mice modeling not only vEDS but also related hADs, allowing the aortic-rupture-force-focused comparison of mouse models. Furthermore, aneurysm progression alone may not be a sufficient read-out for aortic rupture, as antihypertensive drugs reducing aortic dilatation might not strengthen the weakened aortic wall. Our results may enable identification of improved medical therapies of hADs., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes., Design: Prospective cross-sectional study., Methods: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle., Results: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: Extracorporeal cardiopulmonary resuscitation (ECPR) is an effective treatment for out-of-hospital cardiac arrest and refractory ventricular fibrillation. Despite the success of this intervention, trauma is a potential complication that may adversely impact patient outcomes. This study assessed the incidence and impact of trauma in patients who underwent ECPR. We hypothesized that all trauma incurred until the conclusion of ECPR would have a significant negative effect on survival and neurological outcomes., Methods: This retrospective observational study examined all ECPR patients admitted to a tertiary emergency medical center between January 2015 and December 2021. All patients underwent pan-scan computed tomography (CT) before admission to the intensive care unit. The head and body trauma were assessed from CT images taken after ECPR. Trauma was defined as all trauma affecting post-ECPR management. In other words, all trauma caused by collapse, trauma caused by resuscitative actions such as chest compressions, and vascular injuries associated with ECPR were included. Univariate analysis of neurological prognosis and 30-day survival due to complicated trauma was performed., Results: A total of 189 patients (mean age 55.2 ± 13.4 years; 85.2% male) were included in this study. Four patients (2.1%) had head trauma, and 31 patients (16.4%) had torso trauma. All patients with head trauma died during extracorporeal membrane oxygenation management. In patients with torso trauma, 30-day survival was not significantly different compared with that in those without trauma (31.5% vs. 41.9%, P  = 0.60); good neurological outcomes were almost the same (26.0% vs. 25.8%, P  = 1.00). Approximately half of the patients with torso trauma (48%) underwent transarterial embolization., Conclusion: Patients treated with ECPR can suffer a variety of traumatic injuries from the time of collapse to the establishment of ECMO. Head trauma may be lethal and warrants caution. With appropriate treatment, patients with torso trauma may have an equivalent prognosis to those without traumatic complications., Competing Interests: 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., (© 2024 The Author(s).)

Bovine leukemia virus (BLV) is prevalent worldwide, causing serious problems in the cattle industry. The BLV proviral load (PVL) is a useful index for estimating disease progression and transmission risk. We previously developed a quantitative real-time PCR (qPCR) assay to measure the PVL using the coordination of common motif (CoCoMo) degenerate primers. Here, we constructed a novel duplex BLV-CoCoMo qPCR assay that can amplify two genes simultaneously using a FAM-labeled MGB probe for the BLV LTR gene and a VIC-labeled MGB probe for the BoLA-DRA gene. This liquid duplex assay maintained its original sensitivity and reproducibility in field samples. Furthermore, we developed a dry duplex assay composed of PCR reagents necessary for the optimized liquid duplex assay. We observed a strong positive correlation between the PVLs measured using the dry and liquid duplex assays. Validation analyses showed that the sensitivity of the dry duplex assay was slightly lower than that of the other methods for the detection of a BLV molecular clone, but it showed similar sensitivity to the singleplex assay and slightly higher sensitivity than the liquid duplex assay for the PVL quantification of 82 field samples. Thus, our liquid and dry duplex assays are useful for measuring the BLV PVL in field samples, similar to the original singleplex assay.

The formation of volatile compounds affects the flavor of processed wheat flour products. Herein, the effects of the composition of fatty acid hydroperoxides and the differences in the antioxidant contents among wheat cultivars on the flavor of wheat flour products were clarified. For this purpose, the volatile compounds in wheat flour doughs, LOX activity, fatty acid hydroperoxide composition from fractionated LOX, and antioxidant content were analyzed. Norin61 exhibited a high LOX activity and 9-fatty acid hydroperoxide production. Unsaturated aldehydes derived from 9-fatty acid hydroperoxides contributed significantly to the volatile compound profile of Norin61. Moreover, the lowest lutein content was observed in Norin61 among the analyzed cultivars. The LOX activity and composition of the fatty acid hydroperoxides produced by LOX affected the production of volatile compounds, whereas carotenoids had a suppressive effect. This study provides useful information for product design with the desired flavor for developing various processed wheat flour products., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tomoyuki Narisawa reports financial support was provided by the Tojuro Iijima Foundation for Food Science and Technology. Tomoyuki Narisawa reports financial support was provided by Japan Society for the Promotion of Science., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM for cleared specimens), a low-cost ($20,000-50,000), low-expertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a three-dimensional manner. Academically open-sourced ( https://github.com/dbsb-juntendo/descSPIM ), descSPIM allows routine three-dimensional imaging of cleared samples in minutes. Thus, the dissemination of descSPIM will accelerate biomedical discoveries driven by tissue clearing technologies., (© 2024. The Author(s).)

Background: Cepharanthin ® alone or in combination with glucocorticoid (GC) has been used to treat chronic immune thrombocytopenia (ITP) since the 1990s. Cepharanthine (CEP) is one of the main active components of Cepharanthin ® . The purpose of this study was to investigate the effects of CEP on GC pharmacodynamics on immune cells and analyse the possible action mechanism of their interactions., Methods: Peripheral blood mononuclear cells (PBMCs), T lymphocytic leukemia MOLT-4 cells and daunorubicin resistant MOLT-4 cells (MOLT-4/DNR) were used to evaluate the pharmacodynamics and molecular mechanisms. Drug pharmacodynamics was evaluated by WST-8 assay. P-glycoprotein function was examined by rhodamine 123 assay. CD4 + CD25 + Foxp3 + regulatory T cells and Th1/Th2/Th17 cytokines were detected by flow cytometry. P-glycoprotein expression and GC receptor translocation were examined by Western blot., Results: CEP synergistically increased methylprednisolone (MP) efficacy with the suppressive effect on the cell viability of PBMCs. 0.3 and 1 μM of CEP significantly inhibited P-glycoprotein efflux function of CD4 + cells, CD8 + cells, and lymphocytes (P<0.05). 0.03~3 μM of CEP also inhibited the P-glycoprotein efflux function in MOLT-4/DNR cells in a concentration-dependent manner (P<0.001). However, 0.03~3 μM of CEP did not influence P-glycoprotein expression. 0.03~0.3 μM of CEP significantly increased the GC receptor distribution from the cytoplasm to the nucleus in a concentration-dependent manner in MOLT-4/DNR cells. The combination did not influence the frequency of CD4 + , CD4 + CD25 + and CD4 + CD25 + Foxp3 + T cells or the secretion of Th1/Th2/Th17 cytokines from PBMCs. In contrast, CEP alone at 1 μM decreased the percentage of CD4 + T cell significantly (P<0.01). It also inhibited the secretion of IL-6, IL-10, IL-17, TNF-α, and IFN-γ., Conclusions: CEP synergistically promoted MP pharmacodynamics to decrease the cell viability of the mitogen-activated PBMCs, possibly via inhibiting P-glycoprotein function and potentiating GC receptor translocation. The present study provides new evidence of the therapeutic effect of Cepharanthin ® alone or in combination with GC for the management of chronic ITP., (© 2024. The Author(s).)

Hypertension is the greatest and the most preventable risk factor for cardiovascular disease. Excessive sodium (Na) intake and insufficient potassium (K) intake have been identified as risk factors for hypertension. Socioeconomic status (SES) may be related to diet quality. In Japan, few studies have examined the relationship between urinary Na and K excretion and SES in adults, and there are no studies in children. In 2014, 1944 children (1382 households) in all public elementary schools in Yaese town, Okinawa, Japan were recruited to participate in a study. Casual urine specimens were collected to estimate 24-h urinary Na and K excretion and urinary Na/K ratio. Mother's educational background and household incomes were assessed and used as indicators of SES. A total of 236 pairs of children and their mothers were analyzed in this study. Urinary Na and K excretion were not significantly related to educational levels of mothers and household incomes in children. On the other hand, in mothers, lower household income group had higher 24-h estimated urinary Na excretion and urinary Na/K ratio than other groups. There was no significant difference between urinary excretion and educational levels in mothers. Household income disparities in urinary levels seen in mothers were not seen in children. There may be some factors that moderate the dietary inequalities in children., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Intrahepatic cholangiocarcinoma (ICC) has a high recurrence rate and a poor prognosis. Thus, the development of effective treatment and prognostic biomarkers is required. High expression of diacylglycerol kinase alpha (DGKα) is a prognostic factor for the recurrence of hepatocellular carcinoma. However, the relationship between DGKα expression and prognosis in ICC has not been reported., Methods: Immunohistochemistry (IHC) with anti-DGKα antibody was performed on surgical specimens of ICC (n = 69). First, DGKα expression in cancer cells was qualitatively classified into four groups (-, 1+, 2+, 3+) and divided into two groups (DGKα- and DGKα+1 + to 3+). The relationship between clinical features and DGKα expression was analyzed. Second, Ki-67 expression was evaluated as a cell proliferation marker. The number of Ki-67-positive cells was counted, and the relationship with DGKα expression was examined., Results: DGKα IHC divided the patients into a DGKα+ group (1+: n = 15; 2+: n = 5; 3+: n = 5) and a DGKα- group (-: n = 44). In the DGKα+ group, patients were older and had advanced disease. Both overall survival and recurrence-free survival (RFS) were significantly worse in the DGKα+ patients. DGKα+ was identified as an independent prognostic factor for RFS by multivariate analysis. Furthermore, the number of Ki-67-positive cells increased in association with the staining levels of DGKα., Conclusion: Pathological DGKα expression in ICC was a cancer proliferation marker associated with recurrence. This suggests that DGKα may be a potential therapeutic target for ICC., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Rewarming therapies for accidental hypothermia (AH) include extracorporeal membrane oxygenation (ECMO) and non-ECMO related (conventional) therapies. However, there are limited data available to inform the selection of conventional rewarming therapy. The aim of the present study was to explore what patients' factors and which rewarming therapy predicted favorable prognosis., Methods: This study is a secondary analysis of the Intensive Care with Extra Corporeal membrane oxygenation Rewarming in Accidentally Severe Hypothermia (ICE-CRASH) study, a multicenter prospective, observational study conducted in Japan. Enrolled in the ICE-CRASH study were patients aged ≥18 years with a core temperature of ≤32 °C who were transported to the emergency departments of 36 tertiary care hospitals in Japan between 1 December 2019 and 31 March 2022, among whom those who were rewarmed with conventional rewarming therapy were included in the present study. Logistic regression analysis was performed with 28-day survival as the objective variable; and seven factors including age, activities of daily living (ADL) independence, sequential organ failure assessment (SOFA) score, and each rewarming technique as explanatory variables. We performed linear regression analysis to identify whether each rewarming technique was associated with rewarming rate., Results: Of the 499 patients enrolled in the ICE-CRASH study, 371 were eligible for this secondary analysis. The median age was 81 years, 50.9% were male, and the median initial body temperature was 28.8 °C. Age (odds ratio [OR]: 0.97, 95% confidence interval [CI]: 0.94-1.00) and SOFA score (OR: 0.73, 95% CI: 0.67-0.81) were associated with lower survival, whereas ADL independence (OR: 2.31, 95% CI: 1.15-4.63) was associated with higher survival. No conventional rewarming therapy was associated with 28-day survival. Hot bath was associated with a high rewarming rate (regression coefficient: 1.14, 95% CI: 0.75-1.53)., Conclusion: No conventional rewarming therapy was associated with improved 28-day survival, which suggests that background factors such as age, ADL, and severity of condition contribute more to prognosis than does the selection of rewarming technique., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Whether and how the transfusion volume should be limited in resuscitation after trauma remains unclear. We investigated the association between transfusion volume and survival outcome following trauma., Methods: Using the Japan Trauma Data Bank (2019-2021), we identified patients 18 years or older who received balanced blood transfusion within the first 24 hours of injury. We evaluated the association between the total number of red blood cell (RBC) units transfused and survival at discharge using logistic regression analysis and generalized additive model. Subgroup analyses based on patient characteristics were performed., Results: Overall, 5,123 patients from 165 hospitals were eligible for analysis. The transfusion volume was significantly associated with survival rate. Compared with that of patients receiving 4 to 9 RBC units, the within-hospital odds ratios (95% confidence interval) for survival at discharge were 0.62 (0.55-0.75), 0.32 (0.25-0.40), and 0.15 (0.12-0.20) for those receiving 10 to 19, 20 to 29, and ≥30 U, respectively. The probability of survival decreased consistently without any discernible threshold; however, the survival rates remained >40% and >20% even in patients receiving 50 and 80 RBC units, respectively. Significant interactions were observed between the number of RBC units transfused and each subgroup for survival at discharge., Conclusion: The probability of survival consistently diminished as the transfusion volume increased. The absence of a threshold and lack of exceedingly low probability of survival support massive transfusion when clinicians perceive ongoing transfusion as beneficial. The unique context of each clinical situation must be considered in decision making., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to evaluate the impact of shear stress on surgery-related sacral pressure injury (PI) after laparoscopic colorectal surgery performed in the lithotomy position. We included 37 patients who underwent this procedure between November 2021 and October 2022. The primary outcome was average horizontal shear stress caused by the rotation of the operating table during the operation, and the secondary outcome was interface pressure over time. Sensors were used to measure shear stress and interface pressure in the sacral region. Patients were divided into two groups according to the presence or absence of PI. PI had an incidence of 32.4%, and the primary outcome, average horizontal shear stress, was significantly higher in the PI group than in the no-PI group. The interface pressure increased over time in both groups. At 120 min, the interface pressure was two times higher in the PI group than in the no-PI group (PI group, 221.5 mmHg; no-PI group, 86.0 mmHg; p < 0.01). This study suggested that shear stress resulting from rotation of the operating table in the sacral region by laparoscopic colorectal surgery performed in the lithotomy position is the cause of PI. These results should contribute to the prevention of PI., (© 2024. The Author(s).)

We synthesized a perovskite-type RbNbO 3 at 1173 K and 4 GPa from non-perovskite RbNbO 3 and investigated its crystal structure and properties towards ferroelectric material design. Single-crystal X-ray diffraction analysis revealed an orthorhombic cell in the perovskite-type structure (space group Amm 2, no. 38) with a = 3.9937(2) Å, b = 5.8217(3) Å, and c = 5.8647(2) Å. This non-centrosymmetric space group is the same as the ferroelectric BaTiO 3 and KNbO 3 but with enhanced distortion. Structural transition from orthorhombic to two successive tetragonal phases (Tetra1 at 493 K, Tetra2 at 573 K) was observed, maintaining the perovskite framework before reverting to the triclinic ambient phase at 693 K, with no structural changes between 4 and 300 K. The first transition is similar to that of KNbO 3 , whereas the second to Tetra2, marked by c -axis elongation and a significant c p / a p ratio jump (from 1.07 to 1.43), is unique. This distortion suggests a transition similar to that of PbVO 3 , where an octahedron's oxygen separates along the c -axis, forming a pyramid. Ab initio calculations simulating negative pressure like thermal expansion predicted this phase transition ( c p / a p = 1.47 at -1.2 GPa), aligning with experimental findings. Thermal analysis revealed two endothermic peaks, with the second transition entailing a greater enthalpy change and volume alteration. Strong second harmonic generation signals were observed across Ortho, Tetra1, and Tetra2 phases, similar to BaTiO 3 and KNbO 3 . Permittivity increased during the first transition, although the second transition's effects were limited by thermal expansion-induced bulk sample collapse. Perovskite-type RbNbO 3 emerges as a promising ferroelectric material.

Background: The ONO-4059-02 phase 1/2 study showed favorable efficacy and acceptable safety profile of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, for relapsed/refractory primary central nervous system lymphoma (PCNSL). Here, we report the long-term efficacy and safety after a 3-year follow-up., Methods: Eligible patients were aged ≥ 20 years with histologically diagnosed PCNSL and KPS of ≥ 70. Patients received oral tirabrutinib once daily at 320 or 480 mg, or 480 mg under fasted conditions., Results: Between October 19, 2017, and June 13, 2019, 44 patients were enrolled: 33 and 9 had relapsed and refractory, respectively. The 320, 480, and 480 mg fasted groups included 20, 7, and 17 patients, respectively. The median follow-up was 37.1 months. The overall response rate was 63.6% (95% CI: 47.8-77.6) with complete response (CR), unconfirmed CR, and partial response in 9, 7, and 12 patients, respectively. The median duration of response (DOR) was 9.2 months, with a DOR rate of 19.8%; the median progression-free survival (PFS) and median overall survival (OS) were 2.9 months and not reached, respectively, with PFS and OS rates of 13.9% and 56.7%, respectively. Adverse events occurred in 38 patients (86.4%): grade ≥ 3 in 23 (52.3%) including 1 patient with grade 5 events. KPS and quality of life (QoL) scores were well maintained among patients receiving long-term treatment., Conclusions: The results demonstrated the long-term clinical benefit of tirabrutinib, with deep and durable response in a subset of patients and acceptable safety profile, while KPS and QoL scores were maintained., Competing Interests: All authors received support for developing the manuscript, which includes funding, medical writing, and article processing charge. HY reports honoraria from Ono, Chugai, Fujifilm, and Novocure global. YN reports grants from Chugai, Sumitomo Pharma, Eisai, Otsuka, SBI, AbbVie, Daiichi Sankyo, Stella Pharma, and Meiji Seika; honoraria from Chugai, Sumitomo Pharma, Eisai, Otsuka, SBI, AbbVie, Daiichi Sankyo, Stella Pharma, and Meiji Seika. MN reports grants from Chugai, MSD, Nippon Kayaku, Bristol Myers Squibb, Pfizer, Takeda, Shionogi, Kyowa Kirin, Teijin Pharma, Asahi Kasei Medical, HOYA Technosurgical, AbbVie, Eisai, Daiichi Sankyo, Otsuka, Astellas, Tsumura, Sanofi, Mitsubishi Tanabe Pharma, Sanei, CSF Behring, and Ono; consulting fees from Ono, Nippon Shinyaku, and Novocure; honoraria from Chugai, MSD, Nippon Kayaku, UCB Japan, Sumitomo Pharma, Ono, Ohara, AbbVie, Eisai, Daiichi Sankyo, Novocure, Bristol Myers Squibb, and Kyowa Kirin; support for attending meetings and/or travel from Ono, Eisai, Denka, Kyowa Kirin, and Nippon Kayaku; Participation on a Data Safety Monitoring Board or Advisory Board in Novocure; and medical writing support from Ono and Chugai. KM reports grants from Chugai, Eisai, Gunze Medical, Otsuka, Nihon Medi-Physics, Gunze, Stryker Japan, Kyowa Kirin, MSD, Teijin Pharma, AbbVie, Daiichi Sankyo, Novocure, HOYA Technosurgical, Ohara, and CSL Behring; and honoraria from Ono and Chugai. YA reports grants from Philips, Otsuka, Chugai, Nihon Medi-Physics, Daiichi Sankyo, Stryker, Eisai, Japan Blood Products Organization, Ono, Taiho, Sumitomo Pharma, Astellas, Incyte Biosciences, and Servier; and honoraria for lectures from Nippon Kayaku, Novocure, UCB Japan, Ono, Brainlab, Merck, Chugai, Eisai, Daiichi Sankyo, Carl Zeiss, and Nihon Medi-Physics. KA reports honoraria and support for attending meetings and/or travel from Ono. NF reports grants from Ono, Bayer, Chugai, Celgene, and Genmab and Incyte; honoraria from AstraZeneca, Bristol Myers Squibb, Chugai, CSL Behring, Sumitomo Pharma, Eisai, Janssen, Kyowa Kirin, Nippon Shinyaku, Novartis, Ono, Otsuka, Sanofi, SymBio, Takeda, and Zenyaku; and participation on a data safety monitoring board in Huya Japan and an advisory board in AstraZeneca, AbbVie, Eli Lilly, Genmab, and Novartis. KS reports honoraria from Daiichi Sankyo, Eisai, Meiji Seika Pharma, Bristol Myers Squibb, Novartis, Ono, and Nobel Pharma. AA is employed in Ono and holds stocks of Ono. RN reports grants from MSD, Eisai, AbbVie, and Chugai; and consulting fee from Novocure; honoraria from AbbVie, Chugai, Daiichi Sankyo, Eisai, Novocure, and Ono., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: The treatment of patients with infective endocarditis (IE) who have preoperative cerebral complications remains less understood. Therefore, this study aimed to retrospectively evaluate the clinical outcomes of patients with acute IE based on preoperative intracranial findings., Methods: Of 32 patients with acute IE treated at our hospital between August 2015 and March 2022, 31 patients of whom preoperative intracranial imaging evaluation was available were included in our analysis and compared with those with and without intracranial findings. We controlled the mean arterial blood pressure and activated clotting time (ACT) to prevent abnormally high perfusion pressures and ACTs during cardiopulmonary bypass (CPB). The preoperative background, and postoperative courses focusing on postoperative brain complications were reviewed., Results: Among the 31 patients, 20 (65%) had preoperative imaging findings. The group with intracranial findings was significantly older, with more embolisms in other organs, positive intraoperative pathology findings, and longer CPB times. A new cerebral hemorrhage developed postoperatively in one patient without intracranial findings. There were no early deaths; two patients had recurrent infections in each group, and one died because of sepsis in the late phase in the group with intracranial findings., Conclusions: Positive intracranial findings indicated significantly active infectious conditions preoperatively but did not affect the postoperative course. Patients without preoperative cerebral complications can develop serious cerebral hemorrhage. Although meticulous examination of preoperative cerebral complications in all patients with IE is essential, a strategy should be adopted to prevent cerebral hemorrhage, even in patients without intracranial findings., (© 2024. The Author(s).)

Background/aims: This study aimed to investigate and compare the efficacy and safety of first-line and second-line selective laser trabeculoplasty (SLT) in Japanese patients with normal-tension glaucoma (NTG)., Methods: 100 patients with NTG were enrolled in this study. Patients were treated with SLT as a first-line or second-line treatment for NTG. Main outcome measures were intraocular pressure (IOP) reduction rate, outflow pressure improvement rate (ΔOP), success rate at 1 year and complications. Success was defined as ΔOP≥20% (criterion A) or an IOP reduction ≥20% (criterion B) without additional IOP-lowering eye-drops, repeat SLT or additional glaucoma surgeries. The incidence of transient IOP spike (>5 mm Hg from the pretreatment IOP), conjunctival hyperaemia, inflammation in the anterior chamber and visual impairment due to SLT were assessed., Results: A total of 99 patients (99 eyes) were initially enrolled in this study, including 74 eyes assigned to the first-line SLT group and 25 eyes to the second-line SLT group. The mean IOP of 16.3±2.1 mm Hg before SLT decreased by 17.1%±9.5% to 13.4±1.9 mm Hg at 12 months after SLT in the first-line group (p<0.001), and the mean IOP of 15.4±1.5 mm Hg before SLT decreased by 12.7%±9.7% to 13.2±2.0 mm Hg at 12 months after SLT (p=0.005) in the second-line group. Both groups showed significant reductions in IOP. Higher pre-SLT IOP and thinner central corneal thickness were associated with greater IOP reduction. The success rate at 1 year was higher in the first-line compared with the second-line group, with lower pretreatment IOP and the use of IOP-lowering medication before SLT being associated with treatment failure. Most post-treatment complications were minor and transient., Conclusions: SLT may be an effective and safe treatment option for NTG, as either a first-line or second-line treatment., Trial Registration Number: The study was registered in the UMIN-CTR (UMIN Test ID: UMIN R000044059)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To gain insights into the mechanisms of free surface oscillation in a rotating mixing container, we observe the free surface deformation and measure the torque acting on the bar. The container was half-filled with liquids. Periodic surface oscillation occurs. At the rotational speed where the amplitude of the oscillation reaches its maximum, the time-averaged torque also takes the local maximum values. To account for the sloshing mechanism, an equation of motion is derived using the Lagrangian mechanics; we found that the sloshing occurs when the collision frequency of bar on the surface is consistent with the natural frequency of the system and the damping coefficient is sufficiently smaller than unity. The time-averaged torque increases when the sloshing becomes violent. We conclude that the hydrodynamics of oscillation is successfully modeled using point-mass mechanics, and thus we can reasonably capture the rotation speed at which violent oscillation occurs., (© 2024. The Author(s).)

We investigated the wing vein network topology in fruit flies and observed that the posterior cross vein (PCV) disrupts the symmetry of the entire network. The fluidic engineering function of this vein's disposition remains unexplored although the wing vein network is known to transport blood. We examined the fluid mechanical effects of the PCV's disposition on this blood-transporting network through numerical simulations involving the removal and rearrangement of the vein, avoiding impractical physical manipulation. We characterised the geometry of each wing membrane cell, a portion of the wing membrane surrounded by a group of veins, by determining the ratio of its surface area to the contact area with the veins. We considered this ratio in association with the flow velocities of seeping water from the blood within the veins to the membrane and evaporating water from the membrane, based on the mass conservation law. We observed that the division of a membrane cell by the PCV maximises the ratio of the areas in the divided cell on the wing-tip side by virtually shifting this vein's connections in our geometric membrane model. We derived blood flow rate and pressure loss within the venous network from their geometry, using an analogy of the venous network with a circuit consisting of hydraulic resistors based on Kirchhoff and Ohm's laws. The overall pressure loss in the network decreased by 20% with the presence of the PCV functioning as a paralleled hydraulic resistor. By contrast, any other cross-vein computationally arranged on another membrane cell as the PCV's substitution did not exhibit a larger reduction in the pressure loss. Overall, our numerical analyses, leveraging geometry and a circuit analogy, highlighted the effects of the PCV's presence and position on the blood-transporting vein network., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sugiyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: In clinical practice, teicoplanin (TEIC) is typically administered at a trough concentration of 15-40 µg/mL. TEIC has a protein binding rate of approximately 90%, and its concentration rarely exceeds 40 µg/ml. Nevertheless, an increase in the free blood trough concentration may result in renal dysfunction. However, the relationship between the free blood trough concentration and the occurrence of renal dysfunction remains unclear. This study aimed to examine the impact of the predicted free blood concentration on the development of renal dysfunction., Methods: This retrospective study included patients who underwent TEIC and had at least one trough concentration measurement. The association between the frequency of renal dysfunction occurrence and the predicted free blood concentration was evaluated using the following equation: free TEIC concentration = total TEIC concentration/(1 + 1.78 × serum albumin level)., Results: Of the 170 patients included in this study, 18% (31/170) developed renal dysfunction. The predicted free trough concentration was significantly higher in the renal dysfunction onset group than in the nononset group. However, the total trough concentration was not significantly associated with the development of renal dysfunction. The odds ratio for developing renal dysfunction was 4.5 (95% confidence interval, 1.9-10.5; P < 0.001) when the predicted free trough concentration was > 4.0 µg/mL., Conclusion: Elevated free trough concentrations of TEIC were associated with an increased risk of renal dysfunction. Controlling the increase in the predicted free blood concentration may effectively prevent the development of renal dysfunction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Oral drug absorption involves drug permeation across the apical and basolateral membranes of enterocytes. Although transporters mediating the influx of anionic drugs in the apical membranes have been identified, transporters responsible for efflux in the basolateral membranes remain unclear. Monocarboxylate transporter 6 (MCT6/SLC16A5) has been reported to localize to the apical and basolateral membranes of human enterocytes and to transport organic anions such as bumetanide and nateglinide in the Xenopus oocyte expression system; however, its transport functions have not been elucidated in detail. In this study, we characterized the function of MCT6 expressed in HEK293T cells and explored fluorescent probes to more easily evaluate MCT6 function. The results illustrated that MCT6 interacts with CD147 to localize at the plasma membrane. When the uptake of various fluorescein derivatives was examined in NaCl-free uptake buffer (pH 5.5), the uptake of 5-carboxyfluorescein (5-CF) was significantly greater in MCT6 and CD147-expressing cells. MCT6-mediated 5-CF uptake was saturable with a K m of 1.07 mM and inhibited by several substrates/inhibitors of organic anion transporters and extracellular Cl ion with an IC 50 of 53.7 mM. These results suggest that MCT6 is a chloride-sensitive organic anion transporter that can be characterized using 5-CF as a fluorescent probe., 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 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Home healthcare is important for allowing patients to live their lives. However, home-care bedridden patients often experience pressure ulcers in the lower extremities, which can lead to life-threatening infections requiring decisions on the need for amputation. We herein report a patient with an infected lower-limb pressure ulcer with a history of spinal injury. The patient, his family, and the home-care physician repeatedly shared decision-making to deliver home-based treatment instead of amputation. Administration of wound dressing, AQUACEL ® Ag, led to complete epithelialization. Such shared decision-making and dressing were feasible in a home-care setting and broadened its scope.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively., (© 2024. The Author(s).)

Aim: FibCare ® is a novel point-of-care testing device enabling prompt evaluation of fibrinogen levels. This study aimed to investigate the accuracy of FibCare ® at a tertiary emergency department., Methods: Blood specimens obtained at a tertiary emergency medical center between October 1, 2021, and April 30, 2023, were evaluated. The correlation between the fibrinogen levels assessed via FibCare ® and those via the Clauss method was evaluated using the Spearman's test. The discrepancy between the two measurement methods was assessed according to fibrinogen level and diagnosis., Results: A total of 177 specimens from 147 patients were eligible for the analysis. The median age of the patients was 49 years, and 109 (61.6%) were men. The two measurements had statistically significant but moderate correlation ( p  < 0.001, ρ  = 0.76). FibCare ® missed 14 out of 35 cases from patients with hypofibrinogenemia (fibrinogen ≤150 mg/dL assessed by the Clauss method). The discrepancy between the two measurements was significantly greater in specimens with lower fibrinogen levels and those obtained from patients following trauma., Conclusions: FibCare ® , a novel point-of-care testing device, can be compatible with the Clauss method. However, clinicians should be aware of the risk that FibCare ® may underestimate fibrinogen reduction, especially in severe cases and trauma cases., Competing Interests: The authors declare no conflict of interests for this article., (© 2024 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Objectives: Intrapulpal calcifications can occur in the dental pulp of patients with diabetes. We focused on the association between ectopic calcifications in the dental pulp and advanced glycation end products (AGEs) in Spontaneously Diabetic Torii (SDT)-fatty rats, an obese type 2 diabetic rat model, to determine the mechanism of calcification with pulp stone in the dental pulp., Materials and Methods: Pathologic calcification in the dental pulp of SDT-fatty rats was observed using electron microscopy and immunohistochemical analysis. Moreover, mechanical analysis of periapical region of molar tooth against occlusal force was performed., Results: In SDT-fatty rats, pathogenic pulpal calcifications occurred during blood glucose elevation after 6 weeks, and granular calcification was observed in the dental pulp after 11 weeks. Pentosidine, a major AGE, and the receptor for AGEs were strongly expressed in the dental pulp of SDT-fatty rats. S100A8, TNF-α, and IL-6 also showed positive response in the dental pulp of the SDT-fatty rat, which indicated pulpal inflammation. Blood flow disorder and hypoxic dental pulp cells were also observed. In silico simulation, strain from occlusal force concentrates on the root apex., Conclusions: Glycation makes blood vessels fragile, and occlusal forces damage the vessels mechanically. These are factors for intrapulpal calcification of diabetes., (© 2023 Wiley Periodicals LLC.)

A new nondestructive inspection method, the magnetic hammer test (MHT), which uses a compact and highly sensitive tunnel magnetoresistance (TMR) sensor, is proposed. This method complements the magnetic flux leakage method and eliminates the issues of the hammer test. It can therefore detect weak magnetic fields generated by the natural vibration of a pipe with a high signal-to-noise ratio. In this study, several steel pipes with different wall thicknesses were measured using a TMR sensor to demonstrate the superiority of MHT. The results of the measurement show that wall thickness can be evaluated with the accuracy of several tens of microns from the change in the natural vibration frequency of the specimen pipe. The pipes were also inspected underwater using a waterproofed TMR sensor, which demonstrated an accuracy of less than 100 μm. The validity of these results was by simulating the shielding of magnetic fields and vibration of the pipes with the finite element method (FEM) analysis. The proposed noncontact, fast, and accurate method for thickness testing of long-distance pipes will contribute to unmanned, manpower-saving nondestructive testing (NDT) in the future.

This study aims to determine the cutoff values for the compound muscle action potential (CMAP) stimulus in anatomically identified anterior (motor nerve) and posterior roots (sensory nerve) during cervical intradural extramedullary tumor surgery. The connection between CMAP data from nerve roots and postoperative neurological symptoms in thoracolumbar tumors was compared with data from cervical lesions. The participants of the study included 22 patients with intradural extramedullary spinal tumors (116 nerve roots). The lowest stimulation intensity to the nerve root at which muscle contraction occurs was defined as the minimal activation intensity (MAI) in the CMAP. In cervical tumors, the MAI was measured after differentiating between the anterior and posterior roots based on the anatomical placement of the dentate ligament and nerve roots. The MAIs for 20 anterior roots in eight cervical tumors were between 0.1 and 0.3 mA, whereas those for 19 posterior roots were between 0.4 and 2.0 mA. The cutoff was <0.4 mA for both the anterior and posterior roots, and sensitivity and specificity were both 100%. In thoracolumbar tumors, the nerve root was severed in 12 of 14 cases. All MAIs were determined to be at the dorsal roots as their scores were higher than the cutoff and did not indicate motor deficits. The MAIs of the anatomically identified anterior and posterior root CMAPs were found to have a cutoff value of <0.4 mA in the cervical lesions. Similar MAI cutoffs were also applicable to thoracolumbar lesions. Thus, CMAP may be useful in detecting anterior and posterior roots in spinal tumor surgery.

Purpose: To investigate factors associated with the severity of prelaminar schisis (PLS) in heathy subjects and glaucoma patients., Design: Prospective cross-sectional study., Methods: A total of 217 eyes of 217 subjects (110 normal eyes and 107 open angle glaucoma eyes) were studied. Frequency and severity of PLS were compared between normal and glaucomatous eyes. Multivariate logistic models were used to assess factors associated with the severity of PLS. Factors considered were age, axial length, glaucomatous damage indices, Bruch membrane opening (BMO) and anterior scleral canal opening parameters, tractional forces (posterior vitreous staging and presence of Bergmeister papilla), circumpapillary choroidal thickness, lamina cribrosa (LC) parameters, and peripapillary scleral (PPS) angle., Results: The frequency of PLS was 70.9% in normal eyes and 72.0% in glaucomatous eyes. There was no difference in frequency and severity between the groups. The presence of Bergmeister papilla was the strongest predictor of a more severe PLS in both normal and glaucomatous eyes (odds ratio [OR] + 9.78, 12.5; both P < .001). A larger PPS angle in normal eyes (OR = 1.19; P = .003) and a larger BMO area and a deeper LC depth in glaucomatous eyes (OR = 1.08, 1.05; both P = .038) were associated with severity of PLS., Conclusions: The severity of PLS was strongly associated with the presence of Bergmeister papilla, suggesting a traction-related phenomenon. Correlation of PLS severity with larger BMO area and deeper LC depth, which are optic nerve head structures associated with glaucoma, suggested its possible relationship with glaucomatous damage., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background/aim: The efficacy of systemic therapy for unresectable small bowel adenocarcinoma that is refractory to fluoropyrimidines and oxaliplatin has not yet been established because of the rarity of this cancer. Although immunotherapy with anti-PD-1 antibodies has shown robust efficacy in the treatment of esophagogastric adenocarcinoma, its effectiveness in small bowel adenocarcinoma remains unclear., Case Report: In the first case, a 75-year-old man was diagnosed with metastatic moderately differentiated adenocarcinoma of the jejunum with stable microsatellite instability. After receiving multiple lines of therapy, including fluoropyrimidines plus oxaliplatin, irinotecan, and paclitaxel, the patient was treated with nivolumab and achieved a partial response that lasted for 12 months. In the second case, a 65-year-old man was diagnosed with an unresectable locally advanced duodenal adenocarcinoma. High microsatellite instability was confirmed by polymerase chain reaction-based testing. After showing resistance to 5-fluorouracil and oxaliplatin, the patient received nivolumab and ipilimumab therapy. Although therapy was discontinued because of immune-related colitis and skin rash, a partial response was achieved., Conclusion: Treatment with immune checkpoint inhibitors is effective for refractory small bowel adenocarcinoma, irrespective of the microsatellite status., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)