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Previous reports focusing on cefiderocol susceptibility against Stenotrophomonas maltophilia have included a large number of noninvasive or colonized isolates, and data focusing on invasive S. maltophilia strains are still lacking. We retrospectively investigated the cefiderocol susceptibility of stored S. maltophilia strains that caused bacteremia at two Japanese hospitals. The MIC 50 and MIC 90 were 0.06 μg/mL and 0.25 μg/mL, respectively, while the susceptibility rate was 99.3% (current CLSI breakpoint criteria). Our results provide the MIC distribution of bacteremic S. maltophilia isolates in Japan and show the preserved cefiderocol susceptibility of S. maltophilia among clinically invasive pathogenic strains., Competing Interests: Declarations. Ethical approval: Not applicable. This article does not contain any studies with human participants or animals performed by any of the authors. Consent to publish: The authors consent to the publication of the manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Skeletal muscle loss has been identified as a prognostic factor in patients with unresectable hepatocellular carcinoma (uHCC) undergoing treatment with lenvatinib (LEN). While atezolizumab plus bevacizumab (ATZ-BEV) is recommended as first-line therapy for uHCC, the impact of skeletal muscle loss in these patients remains unclear. Methods: We enrolled 97 patients treated with either LEN or ATZ-BEV as their first-line therapy and divided them into two groups based on the presence or absence of a low psoas muscle index (low PMI) before treatment. We compared patient characteristics and overall survival (OS) between the groups. Additionally, we investigated the transition of the PMI during drug therapy, specifically before treatment, at the initial evaluation, and after the end of treatment. Results: Seventy percent of patients in the LEN group and seventy-one percent in the ATZ-BEV group had a low PMI. Multivariate analysis across all patients revealed a low PMI (hazard ratio [HR] 3.25, p = 0.0004) as a prognostic factor for OS. The PMI decreased more in the LEN group compared to the ATZ-BEV group. In the Barcelona Clinic Liver Cancer-C group, the OS of ATZ-BEV therapy was significantly better than that of LEN therapy when a low PMI was present ( p = 0.046). Conclusions: A low PMI emerges as a significant prognostic factor in uHCC patients undergoing drug therapy, not only in LEN therapy but also in ATZ-BEV therapy. Additionally, ATZ-BEV therapy may be more favorable for sarcopenic patients with advanced HCC stages.

Introduction: Xanthogranulomatous prostatitis is a very rare benign inflammatory lesion of the prostate that may be similar to prostatic carcinoma in clinical presentation and radiological characteristics., Case Presentation: A 77-year-old man was admitted to our hospital because of high prostate-specific antigen level. Magnetic resonance imaging showed a 6.5 cm in diameter multifocal mass with hemorrhage at the base of the left lobe of the prostate. Biopsy was performed. Histopathological examination revealed no evidence of malignancy. After biopsy, he developed recurring fever, so the patient was treated with open suprapubic tumor resection to control infection. Pathological examination revealed xanthogranulomatous prostatitis., Conclusion: It is necessary to diagnose xanthogranulomatous prostatitis by cooperation between urologists and pathologists, and consider xanthogranulomatous prostatitis as a differential diagnosis. Treatment should be conservative in principle; however, surgical intervention may be necessary., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Background: Hypoxia plays a crucial role in regulating various cellular functions, including ion-transport mechanisms in the kidney. The sodium-chloride co-transporter (NCC) is essential for sodium reabsorption in the distal convoluted tubule (DCT). However, the effects of hypoxia on NCC expression and its regulatory pathways remain unclear. We aimed to explore the effects and potential mechanisms of hypoxia on NCC in vitro., Methods: mDCT15 cells were treated with cobalt chloride (CoCl 2 ) at a concentration of 300 μmol/L to induce hypoxia. The cells were harvested at different time points, namely 30 min, 1 h, 6 h, and 24 h, and the expression of NCC and CaMKII-β was analyzed using Western blot., Results: A time-dependent upregulation of NCC and CaMKII-β expression in response to CoCl 2 -induced hypoxia. KN93 reversed the effect of CoCl 2 on NCC and phosphorylated NCC expression., Conclusions: Hypoxia, mediated through cobalt chloride treatment, upregulates NCC expression via the CaMKII-β pathway in mDCT15 cells.

Introduction: Changes in facial appearance due to orthognathic surgery are known to improve a patient's postoperative quality of life, however, potential changes in cognitive function are unknown. This study examined the effects of changes in facial appearance due to orthognathic surgery on the sensitivity to self and to outside objects in patients with jaw deformities., Methods: Patients with jaw deformities ( n  = 22) and healthy controls ( n  = 30) were tested at 3 months preoperatively, at 1 month preoperatively, and at 1 month postoperatively to assess their impression of objects (positive, negative, and neutral pictures) and their evaluation of their own face and body., Results: The results showed that changes in facial appearance improved self-evaluation and increased their sensitivity to emotional objects even when the objects were identical. Furthermore, the improving rating for own face was associated with the sensitivity for objects., Discussion: The changes in facial appearance in patients may have helped to clear the sensitivity to these emotional objects. These findings may provide a new indicator of efficacy in orthognathic surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Honma, Yoshiba, Miyamoto, Himi, Haga, Ogura, Maki, Masaoka, Izumizaki and Shirota.)

Pigmentibacter ruber is a newly described bacterium belonging to the Silvanigrellaceae family that was isolated from human blood in 2021. We report the complete genome sequence of a clinical isolate of P. ruber (GTC16762) obtained from a human patient in Japan. Its genome contains a 3.6-Mb chromosome and three circular plasmids., Competing Interests: The authors declare no conflict of interest.

The prompt initiation of stroke treatment significantly influences patient outcomes, highlighting the crucial role of prehospital triage. This study aimed to assess the implementation of the 7-Item Japan Urgent Stroke Triage (JUST-7) score by emergency medical services (EMS) in our region and its effect on emergency transportation for suspected stroke patients. Data were collected from patients suspected of having an acute stroke with a Cincinnati Prehospital Stroke Scale (CPSS) score of 1 or more who were transferred by ambulance within 24 h of symptom onset. Two prehospital stroke scales were employed during different periods: period 1 with CPSS alone (January to December 2020) and period 2 with both CPSS and JUST-7 (January 2021 to March 2023). On-scene time data were obtained from the EMS crews, and data regarding the final diagnosis of patients and their outcomes were obtained from the respective hospitals to which the patients were transferred. These data were compared between periods 1 and 2 and between the CPSS and JUST-7. The results revealed that additional evaluation with JUST-7 did not affect ambulance transport time. The CPSS+JUST-7 approach demonstrated higher specificity in identifying stroke and major artery occlusion than with the CPSS alone; however, an appropriate cut-off value needs to be considered. The JUST-7 achieved a diagnostic concordance rate of 35.9% for the most likely stroke type and 64.0% for the first two most likely types. This research emphasizes the potential of JUST-7 as a valuable addition to prehospital stroke diagnosis protocols. Its flexibility in adapting cut-off values based on regional factors and available medical resources optimizes its utility in diverse healthcare settings. The JUST-7 score is a promising tool for improving patient outcomes through prompt and accurate prehospital assessments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nishiwaki 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.)

Currently, there is no effective treatment for glioblastoma multiforme (GBM), the most frequent and malignant type of brain tumor. The blood-brain (tumor) barrier (BB(T)B), which is composed of tightly connected endothelial cells and pericytes (with partial vasculature collapse), hampers nanomedicine accumulation in tumor tissues. We aimed to explore the effect of nanomedicine size on passive targeting of GBM. A series of size-tunable poly(ethylene glycol) (PEG)-grafted copolymers (gPEGs) were constructed with hydrodynamic diameters of 8-30 nm. Biodistribution studies using orthotopic brain tumor-bearing mice revealed that gPEG brain tumor accumulation was maximized at 10 nm with ∼14 dose %/g of tumor, which was 19 times higher than that in the normal brain region and 4.2 times higher than that of 30-nm gPEG. Notably, 10-nm gPEG exhibited substantially higher brain tumor accumulation than 11-nm linear PEG owing to the prolonged blood circulation property of gPEGs, which is derived from a densely PEG-packed structure. 10 nm gPEG exhibited deeper penetration into the brain tumor tissue than the larger gPEGs did (>10 nm). This study demonstrates, for the first time, the great potential of a nanomedicine downsizing strategy for passive GBM targeting.

This study aimed to ascertain the effects of the shape of stereolithographic models fabricated with a three-dimensional (3D) printer and the use of different types of liquid resin on the dimensional changes of these models over time, to obtain valuable information for determining the period for which such models can be used following fabrication. Stereolithography models with the shape of a large truncated cone or a small truncated cone were fabricated using liquid resin as surgical guides (Group G) or master casts (Group M). (four groups in total, each n = 11). The shapes of all experimental specimens were measured immediately after fabrication and 1 day, 1 week, 2 weeks, 3 weeks, 4 weeks, 2 months, 3 months, 6 months, 1 year, and 1.5 years later. The shape data collected immediately after fabrication were taken as baseline data, and the dimensional changes over time at each timepoint were calculated. No significant change from 1 day to 1 year after fabrication was observed in any of the groups, but the change after 1.5 years was significantly larger than the changes at the other timepoints (p < 0.001). Significantly larger changes were evident in Group M than in Group G at all timepoints (p < 0.001). These results suggested that, from the viewpoint of dimensional stability over time, stereolithographic models should be used within 1 year of fabrication, and that the type of liquid resin used for stereolithographic model fabrication may affect how its dimensions change over time., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

We report the first case of necrotizing fasciitis caused by Pigmentibacter ruber. The isolated strain could not be identified by biochemical characterization or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry but was identified as P. ruber by 16S ribosomal RNA and whole-genome sequencing. Although much remains unknown about the pathogenicity of this bacterial species in humans, it has been shown to cause life-threatening infections such as septicemia and necrotizing fasciitis. Because the isolate was highly resistant to β-lactams, it was difficult to treat with antimicrobial therapy. Thus, further documentation of cases and analyses are required.

Control of circularly polarized light (CPL) is important for next-generation optical communications as well as for investigating the optical properties of materials. In this study, we explore dielectric-sphere oligomers for chiral nanoantenna applications, leveraging the cathodoluminescence (CL) technique, which employs accelerated free electrons for excitation and allows mapping the optical response on the nanoscale. For a certain particle-dimers configuration, one of the spheres becomes responsible for the left-handed circular polarization of the emitted light, while right-handed circular polarization is selectively yielded when the other sphere is excited by the electron beam. Similar patterns are also observed in trimers. These phenomena are understood in terms of optical coupling between the electric and magnetic modes hosted by the dielectric spheres. Our research not only expands the understanding of CPL generation mechanisms in dielectric-sphere oligomer antennas but also underscores the potential of such structures in optical applications. We further highlight the utility of CL as a powerful analytical tool for investigating the optical properties of nanoscale structures as well as the potential of electron beams for light generation with switchable CPL parities., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Compartment syndrome commonly occurs in patients with forearm and lower leg fractures. Compartment syndromes of the gluteal and thigh muscles are less common. It is imperative that compartment syndrome be diagnosed and treated with fasciotomy as soon as possible. However, there are few reports on the diagnosis and treatment strategies for compartment syndromes that occur simultaneously in multiple anatomical regions or in the ipsilateral gluteal region and thigh., Case Presentation: We report on a 76-year-old man who was obliquely crushed under a tree extending from the right forearm to the left groin. He was brought to our emergency room, where he was diagnosed with compartment syndrome of the right forearm and left lower leg and crush syndrome. Emergency fasciotomy was performed. On the day after admission, swelling and tightness of the left gluteal thigh became apparent, and intracompartmental pressures were elevated, which led to an additional diagnosis of these compartment syndromes. A fasciotomy was performed, the gluteal skin incision was made according to the Kocher-Langenbeck approach (one of the posterior approaches for hip fractures), and the thigh was approached by extending the incision laterally. This surgical approach enabled the decompression of the compartments through a single incision and allowed for easier wound treatment and closure., Conclusion: This case highlights the diagnosis and treatment of compartment syndrome in four anatomical regions. Extension of the Kocher-Langenbeck approach to the lateral thigh can be a useful surgical approach for ipsilateral gluteal and thigh compartment syndrome., (© 2024. The Author(s).)

Aims/introduction: To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan., Materials and Methods: Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups., Results: Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively., Conclusions: In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Purpose: This study was conducted to identify the typical sites and patterns of peri-implant bone defects on cone-beam computed tomography (CBCT) images, as well as to evaluate the detectability of the identified bone defects on panoramic images., Materials and Methods: The study population included 114 patients with a total of 367 implant fixtures. CBCT images were used to assess the presence or absence of bone defects around each implant fixture at the mesial, distal, buccal, and lingual sites. Based on the number of defect sites, the presentations of the peri-implant bone defects were categorized into 3 patterns: 1 site, 2 or 3 sites, and circumferential bone defects. Two observers independently evaluated the presence or absence of bone defects on panoramic images. The bone defect detection rate on these images was evaluated using receiver operating characteristic analysis., Results: Of the 367 implants studied, 167 (45.5%) had at least 1 site with a confirmed bone defect. The most common type of defect was circumferential, affecting 107 of the 167 implants (64.1%). Implants were most frequently placed in the mandibular molar region. The prevalence of bone defects was greatest in the maxillary premolar and mandibular molar regions. The highest kappa value was associated with the mandibular premolar region., Conclusion: The typical bone defect pattern observed was a circumferential defect surrounding the implant. The detection rate was generally higher in the molar region than in the anterior region. However, the capacity to detect partial bone defects using panoramic imaging was determined to be poor., Competing Interests: Conflicts of Interest: None, (Copyright © 2024 by Korean Academy of Oral and Maxillofacial Radiology.)

Introduction: Clinically amyopathic dermatomyositis (CADM) with anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) with rapidly progressive interstitial lung disease (RP-ILD) is often refractory for intensive immunosuppression. In this study, we verified the effectiveness and safety of plasma exchange (PEx) for this lethal disease., Methods: We retrospectively examined the clinical course and adverse effect (AE) of 12 patients with anti-MDA5 Ab-positive CADM between January 2017 and December 2021 in our hospital., Results: Five out of six patients treated with simple PEx using fresh frozen plasma or 5% albumin survived with or without home oxygen therapy. Multiple PEx (15-20 times) were required to achieve satisfactory improvement as well as remission of CADM. The AEs caused by PEx were resolved using conventional methods., Conclusion: PEx might be a promising option for controlling the disease activity of anti-MDA5 Ab-positive CADM with severe RP-ILD and may contribute to better survival., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

The success rate of flap tissue reconstruction has increased in recent years owing to advancements in microsurgical techniques. However, complications, such as necrosis, are still more prevalent in diabetic patients compared to non-diabetic individuals, presenting an ongoing challenge. To address this issue, many previous studies have examined vascular anastomoses dilation and stability, primarily concerning surgical techniques or drugs. In contrast, in the present study, we focused on microvascular damage of the peripheral microvessels in patients with diabetes mellitus and the preventative impact of nafamostat mesylate. Herein, we aimed to investigate the effects of hyperglycemia on glycocalyx (GCX) levels in mice with type 2 diabetes. We examined the endothelial GCX (eGCX) in skin flap tissue of 9-12-week-old type 2 diabetic mice (db/db mice) using a perforator skin flap and explored treatment with nafamostat mesylate. The growth rates were compared after 1 week. Heterotype (db/+) mice were used as the control group. Morphological examination of postoperative tissues was performed at 1, 3, 5, and 7 days post-surgery. In addition, db/db mice were treated with 30 mg/kg/day of nafamostat mesylate daily and were evaluated on postoperative day 7. Seven days after surgery, all db/db mice showed significant partial flap necrosis. Temporal observation of the skin flaps revealed a stasis-like discoloration and necrosis starting from the contralateral side of the remaining perforating branch. The control group did not exhibit flap necrosis, and the flap remained intact. In the quantitative assessment of endothelial glycans using lectins, intensity scoring showed that the eGCX in the db/db group was significantly thinner than that in the db/+ group. These results were consistent with the scanning electron microscopy findings. In contrast, treatment with nafamostat mesylate significantly improved the flap engraftment rate and suppressed eGCX injury. In conclusion, treatment with nafamostat mesylate improves the disrupted eGCX structure of skin flap tissue in db/db mice, potentially ameliorating the impaired capillary-to-venous return in the skin flap tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm 3 to 9.6 mm 3 , from 369 µm to 165 µm, respectively ( p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM.

Background: We developed and tested the safety and efficacy of a cosmetic device to improve dark circles using electrical muscle stimulation of the orbicularis oculi muscle., Methods: Overall, 18 participants (36 eyes) were studied. The following five items were evaluated before and after the intervention:(1) the Clinical Dark Circle Score using clinical findings and photographs, (2) transcutaneous oxygen partial pressure (TcPO 2 ) on the lower eyelid, (3) thermography, (4) two-dimensional laser blood flowmetry, and (5) spectrophotometry., Results: The mean score at baseline was 2.0 ± 0.90 (mean ± standard deviation), and that at the end of the study was 1.2 ± 1.0 (Wilcoxon signed-rank sum test, p < 0.0001), indicating a significant reduction. The spectrophotometer showed a significant decrease in a* and L* values before and after use (Wilcoxon signed-rank sum test, p < 0.0001). There was also a weak negative correlation between the change in score and the change in blood flow and TcPO 2 measured using a laser perfusion device (Spearman's rank correlation coefficient, r = -0.32 and -0.39, respectively). Stratified analysis of the baseline score showed a strong negative correlation between the change in score and the change in spectrophotometric a* in the subjects/group with mild periocular dark circles (Spearman's rank correlation coefficient, r = -0.46). Contrastingly, no correlation was observed for any of the measurements in the subjects/group with severe periocular dark circles. After 1 month, no device-related ophthalmic adverse events were observed in any of the participants., Conclusion: Electrical muscle stimulation could improve periocular dark circles, especially in the subjects/group with mild periocular dark circles, and was safe., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Purpose: To investigate the 5-year treatment outcomes of retinopathy of prematurity in infants <500 g birth weight and compare laser and anti-vascular endothelial growth factor therapies., Methods: A multicenter retrospective study comprised 24 eyes of 13 patients treated for Type 1 retinopathy of prematurity, followed for 5 years. Initial treatment was laser and anti-vascular endothelial growth factor in 13 and 11 eyes, respectively. Data collected included sex, birth characteristics, retinopathy of prematurity characteristics at the time of treatment, best-corrected visual acuity (BCVA), spherical equivalent, and astigmatism at 5 years posttreatment., Results: Median BCVA was 0.15 logarithm of the minimum angle of resolution (interquartile range, 0.0-0.5). Snellen BCVA was ≥20/40 in 73% and ≥20/20 in 27% of eyes. Median spherical equivalent was -2.37 (interquartile range, -6.1 to -0.1); 75% had myopia (≤-0.5 D), and 25% had high myopia (≤-6.0 D). Median astigmatism was 1.25 (interquartile range, 0.9-3.0); 46% had ≥1.5 D. Anti-vascular endothelial growth factor-treated eyes showed less myopia ( P < 0.009), with no BCVA or astigmatism difference ( P = 0.997, P = 0.271) compared with laser-treated eyes., Conclusion: One-quarter of the eyes exhibited good visual acuity (Snellen BCVA of ≥20/20) 5 years after retinopathy of prematurity treatment. Refractive errors were common. Anti-vascular endothelial growth factor therapy may be superior to laser therapy in myopic refractive error.

Introduction: Acute kidney injury (AKI), with a fatality rate of 8.6%, is one of the most common types of multiorgan failure in the intensive care unit (ICU). Thus, AKI should be diagnosed early, and early interventions should be implemented. Urinary liver-type fatty acid-binding protein (L-FABP) could aid in the diagnosis of AKI., Methods: In this prospective, single-center, observational study, we included 100 patients with trauma. Urinary L-FABP levels were measured using a semi-quantitative rapid assay kit 6 and 12 h after injury. Negative, weakly positive, and strongly positive urinary L-FABP levels were examined using two protocols. Using protocol 1, measurements were performed at 6 h after injury negative levels were considered "negative," and weakly positive and strongly positive levels were considered "positive." Using protocol 2, strongly positive levels at 6 h after injury were considered "positive," and negative or weakly positive levels at 6 h after injury were considered "positive" if they were weakly positive or positive at 12 h after injury., Results: Fifteen patients were diagnosed with AKI. Using protocol 1, the odds ratio (OR) was 20.55 ( p = 0.001) after adjustment for the injury severity score (ISS), contrast media use, and shock index. When the L-FABP levels at 6 and 12 h were similarly adjusted for those three factors, the OR was 18.24 ( p < 0.001). The difference in ORs for protocols 1 and 2 was 1.619 ( p = 0.04)., Discussion: Associations between urinary L-FABP and AKI can be examined more precisely by performing measurements at 6 and 12 h after injury than only one time at 6 h., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yasuda, Suzuki, Okada, Ishihara, Minamiyama, Kamidani, Kitagawa, Fukuta, Suzuki, Miyake, Yoshida, Tetsuka and Ogura.)

Various cationic polymers are used to deliver polyplex-mediated antisense oligonucleotides (ASOs). However, few studies have investigated the structural determinants of polyplex functionalities in polymers. This study focused on the polymer hydrophobicity. A series of amphiphilic polyaspartamide derivatives possessing various hydrophobic (R) moieties together with cationic diethylenetriamine (DET) moieties in the side chain (PAsp(DET/R)s) were synthesized to optimize the R moieties (or hydrophobicity) for locked nucleic acid (LNA) gapmer ASO delivery. The gene knockdown efficiencies of PAsp(DET/R) polyplexes were plotted against a hydrophobicity parameter, log D 7.3 , of PAsp(DET/R), revealing that the gene knockdown efficiency was substantially improved by PAsp(DET/R) with log D 7.3 higher than -2.4. This was explained by the increased polyplex stability and improved cellular uptake of ASO payloads. After intratracheal administration, the polyplex samples with a higher log D 7.3 than -2.4 induced a significantly higher gene knockdown in the lung tissue compared with counterparts with lower hydrophobicity and naked ASO. These results demonstrate that the hydrophobicity of PAsp(DET/R) is crucial for efficient ASO delivery in vitro and in vivo .

Background: A patient with severe COVID-19 pneumonia had adjunctive acupuncture to improve respiration and facilitate weaning off prolonged mechanical ventilation (MV)., Case: A man in his 40s with COVID-19 was in an advanced critical-care center on symptom day 5 for respiratory failure due to pneumonia requiring MV therapy. He received high-dose corticosteroid pulse therapy, antiviral agents, and multiple antibiotics for complicated bacterial pneumonia and bacteremia. Repeated MV weaning attempts failed, although his pneumonia gradually improved. Then, acupuncture 4 times per week was started to improve his respiration and facilitate MV weaning from day 49 of his symptoms' onset., Results: His weaning-related indices improved, including reductions in respiratory rate and Rapid Shallow Breath Index. His O 2 saturation increased immediately after each acupuncture treatment. The day after the first acupuncture treatment, his MV support was reduced by changing ventilation mode from synchronized intermittent mandatory ventilation mode to continuous positive airway pressure (CPAP) mode during the day without exacerbation of respiratory status. After 3 days of acupuncture, this patient was on CPAP support alone. MV therapy was discontinued completely after 8 days of acupuncture (6th acupuncture treatment)., Conclusions: Acupuncture improved respiration and facilitated MV weaning in a patient with respiratory failure secondary to COVID-19. Adjunctive acupuncture may benefit such patients and others after severe pneumonia. Large cohort studies are needed., Competing Interests: No financial conflicts of interest exist., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Introduction: This study aimed to determine the impact of augmented renal clearance (ARC) on anticoagulation therapy in critically ill patients with coronavirus disease 2019 (COVID-19)., Methods: This retrospective cohort study included adult patients with severe COVID-19 with ARC who had been treated at our hospital between 2020 and 2021. We measured the estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFR CKD-EPI ) every morning, and ARC condition was defined as eGFR CKD-EPI ≥ 130 mL/min/1.73 m 2 . Multivariate regression analysis with Huber-White sandwich estimator was performed to examine the association of unfractionated heparin (UH) dosage between blood test timings with activated partial thromboplastin time (APTT) compared with and without ARC., Results: We identified 38 enrolled patients: seven and 31 in the ARC and non-ARC groups, respectively. In the ARC coexisting condition, a higher dose of UH, which corresponded to the total dose in 24 h from the previous day, was required to achieve the same APTT prolongation, with a significant difference (p < 0.001)., Conclusions: Our study suggests that careful monitoring and consideration of higher UH doses in critically ill patients with COVID-19 is necessary because anticoagulation failure can occur during ARC., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Rhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis mouse model. Further, 750 IU/kg rAT was injected intraperitoneally at 24 and 72 h after the rhabdomyolysis model was established. The mice were euthanized after 96 h for histological analysis. Saline was administered to mice in the control group., Results: Blood tests show elevated serum creatinine, urea nitrogen, and neutrophil gelatinase-associated lipocalin levels in rhabdomyolysis. Loss of tubular epithelial cell nuclei and destruction of the tubular luminal surface structure was observed in the untreated group, which improved with rAT treatment. Immunostaining for Ki-67 showed increased Ki-67-positive nuclei in the tubular epithelial cells in the rAT group, suggesting that rAT may promote tubular epithelial cell regeneration. The microvilli of the brush border of the renal tubules were shed during rhabdomyolysis, and rAT treatment reduced this injury. The vascular endothelial glycocalyx, which is usually impaired by rhabdomyolysis, became functional following rAT treatment., Conclusions: Treatment with rAT suppressed rhabdomyolysis-induced AKI, suggesting that rAT therapy may be a novel therapeutic approach., (© 2024. The Author(s).)

Background: Akt plays diverse roles in humans. It is involved in the pathogenesis of type 2 diabetes mellitus (T2DM), which is caused by insulin resistance. Akt also plays a vital role in human platelet activation. Furthermore, the hippocampus is closely associated with memory and learning, and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without dementia., Aim: To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients., Methods: Platelet-rich plasma (PRP) was prepared from the venous blood of patients with T2DM or age-matched controls. The pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt, p38 mitogen-activated protein (MAP) kinase and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Phosphorylation levels were quantified by densitometric analysis. Hippocampal volume was analysed using a voxel-based specific regional analysis system for Alzheimer's disease on magnetic resonance imaging, which proposes the Z-score as a parameter that reflects hippocampal volume., Results: The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects, whereas the levels of phosphorylated Akt corrected with GAPDH were not. However, this relationship was not observed in the control patients., Conclusion: These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM patients. Our findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Early use of hemostasis strategies, transcatheter arterial embolization (TAE) is critical in cases of pelvic injury because of the risk of hemorrhagic shock and other fatal injuries. We investigated the influence of delays in TAE administration on mortality., Methods: Patients admitted to the Advanced Critical Care Center at Gifu University with pelvic injury between January 2008 and December 2019, and who underwent acute TAE, were retrospectively enrolled. The time from when the doctor decided to administer TAE to the start of TAE (needling time) was defined as "decision-TAE time.", Results: We included 158 patients, of whom 23 patients died. The median decision-TAE time was 59.5 min. Kaplan-Meier curves for overall survival were compared between patients with decision-TAE time above and below the median cutoff value; survival was significantly better for patients with values below the median cutoff value ( p  = 0.020). Multivariable Cox proportional hazards regression analysis revealed that the longer the decision-TAE time, the higher the risk of mortality ( p  = 0.031). TAE duration modified the association between decision-TAE time and overall survival ( p  = 0.109), as shorter TAE duration (procedure time) was associated with the best survival rate ( p for interaction = 0.109)., Conclusion: Decision-TAE time may play a key role in establishing resuscitation procedures in patients with pelvic fracture, and efforts to shorten this time should be pursued., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mizuno, Miyake, Okada, Ishihara, Kanda, Ichihashi, Kamidani, Fukuta, Yoshida, Nagata, Kawada, Matsuo, Yoshida and Ogura.)

Tramadol and duloxetine, reuptake inhibitors of serotonin and noradrenaline, are widely used analgesics. Cytoplasmic serotonin in human platelets reportedly regulates the activity of low-molecular-weight GTP-binding proteins via serotonylation, leading to the modulation of platelet functions. We recently showed that the combination of thrombopoietin and collagen in the low doses synergistically induces human platelet activation via Rac and Rho/Rho-kinase. In the present study, we investigated the effects of tramadol and duloxetine on the synergistic effect, and the mechanism. Tramadol reduced the platelet aggregation and the release of PDGF-AB by the combination of thrombopoietin and collagen in the low doses. The aggregation and the release were also inhibited by duloxetine. Not reboxetine, a specific inhibitor of noradrenaline transporter, but fluvoxamine and sertraline, specific inhibitors of serotonin transporter suppressed the aggregation and the release. Tramadol, duloxetine, fluvoxamine and sertraline but not reboxetine attenuated the levels of GTP-Rac and GTP-Rho, and phospho-cofilin induced by the combination. Taken together, our results strongly suggest that tramadol and duloxetine, not as noradrenaline reuptake inhibitor but as serotonin reuptake inhibitor, suppress the activation of Rac and Rho/Rho-kinase elicited by the combination of subthreshold thrombopoietin and collagen, leading to the attenuation of human platelet activation.

The site of enterohepatic Helicobacter colonization/infection in humans is still unknown. We report microbiologically and histopathologically confirmed H. fennelliae localization in the large intestine in an immunocompromised patient in Japan. This case contributes to better understanding of the life cycle of enterohepatic Helicobacter species.

Background/objective: Acute pancreatitis is an aseptic inflammation caused by pathologically activated pancreatic enzymes and inflammatory mediators produced secondarily by neutrophils and other inflammatory cells and is one of the most difficult diseases to treat. This study aimed to investigate the role of neutrophils in pancreatitis by examining tissue dynamics., Methods: We created a model of caerulein-induced pancreatitis in 12-week-old male granulocyte colony-stimulating factor knockout mice (G-CSF-KO) and wild-type littermate control mice (six intraperitoneal injections of caerulein [80 μg/kg body weight] at hourly intervals for 2 days). Mice were sacrificed 0, 3, 6, 12, 24, 36, 48, 72, and 168 h after caerulein administration and examined histologically., Results: The survival rate after one week of caerulein administration was 100 % in the control mice, whereas it was significantly lower (10 %) in the G-CSF-KO mice. Histological examination revealed significant hemorrhage and inflammatory cell migration in the G-CSF-KO mice, indicating prolonged inflammation., Conclusion: Prolonged inflammation was observed in the G-CSF-KO mice. Tissue cleanup by neutrophils during the acute phase of inflammation may influence healing through the chronic phase., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To compare real-world, long-term outcomes of laser and anti-vascular endothelial growth factor (VEGF) therapies in patients with retinopathy of prematurity (ROP)., Methods: This was a multicentre retrospective study. We included 264 eyes of 139 patients treated for type 1 ROP or aggressive ROP (AROP) who were followed for at least 4 years. Laser treatment was initially performed in 187 eyes (the laser group), and anti-VEGF therapy was initially performed in 77 eyes (the anti-VEGF group). We collected data on sex, birth characteristics, zone, stage, and the presence of plus disease at the time of treatment and best-corrected visual acuity (BCVA), spherical equivalent (SE), and ocular complications (amblyopia and strabismus) in patients aged 4-6 years. We investigated the associations between treatment outcomes (BCVA, SE and the presence of amblyopia and strabismus) and influencing factors, including treatment procedure (anti-VEGF or laser therapy), sex, birth characteristics, zone, stage, and the presence of plus disease, using multivariable analysis and logistic regression analyses., Results: The initial treatment procedure was not associated with any specific treatment outcome. Subgroup analysis of patients with zone I ROP revealed that the anti-VEGF-treated eyes had significantly better BCVA and higher SE than laser-treated eyes (p = 0.004, p = 0.009, respectively). Female patients presented significantly better BCVA, less amblyopia and less strabismus than male patients (p < 0.001, p = 0.029, p = 0.008, respectively)., Conclusions: In zone I ROP, anti-VEGF therapy led to better visual acuity and less myopic refractive error than laser treatment., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Given the widespread prevalence of the coronavirus disease 2019 (COVID-19), oral and neck examinations tend to be avoided in patients with suspected or confirmed COVID-19. This might delay the diagnosis of conditions such as Lemierre's syndrome, which involves symptoms resembling COVID-19-related throat manifestations., Case Presentation: A 24-year-old man without any underlying conditions was diagnosed with COVID-19 7 days before presentation. He was admitted to another hospital 1 day before presentation with severe COVID-19 and suspected bacterial pneumonia; accordingly, he was started on treatment with remdesivir and meropenem. Owing to bacteremic complications, the patient was transferred to our hospital for intensive care. On the sixth day, the patient experienced hemoptysis; further, a computed tomography (CT) scan revealed new pulmonary artery pseudoaneurysms. Successful embolization was performed to achieve hemostasis. In blood cultures conducted at the previous hospital, Fusobacterium nucleatum was isolated, suggesting a cervical origin of the infection. A neck CT scan confirmed a peritonsillar abscess and left internal jugular vein thrombus; accordingly, he was diagnosed with Lemierre's syndrome. The treatment was switched to ampicillin/sulbactam, based on the drug susceptibility results. After 6 weeks of treatment, the patient completely recovered without complications., Conclusion: This case highlights the significance of thorough oral and neck examinations in patients with suspected or diagnosed COVID-19 for the detection of throat and neck symptoms caused by other conditions., (© 2023. The Author(s).)

Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension., (© 2023. Springer Nature Limited.)

Steatohepatitis has been reported to occur after pancreaticoduodenectomy (PD). We report a case of steatohepatitis that arose after PD and led to decompensated liver cirrhosis and hepatocellular carcinoma (HCC). A 65-year-old man underwent PD for suspected intraductal papillary mucinous neoplasm. Eight years after PD, he was diagnosed with liver cirrhosis by laboratory tests and computed tomography. Histological examination of liver biopsy revealed hepatic steatosis, inflammation with ballooning of hepatocytes, and fibrosis, indicating nonalcoholic steatohepatitis as the cause of liver cirrhosis. Ten years after PD, he developed HCC and radiotherapy was performed because of impaired liver function. Intrahepatic metastasis appeared subsequently, but no further treatment could be performed due to decompensated liver cirrhosis. Survival time after PD is being prolonged by improvements in imaging studies and therapeutic strategies. Accordingly, we consider that progression to liver cirrhosis and HCC will occur increasingly in cases such as the present patient, which will become a severe problem in long-term post-PD survival. Therefore, it is necessary to clarify the precise mechanism of steatohepatitis after PD and establish appropriate therapeutic strategies., (© 2023. Japanese Society of Gastroenterology.)

Background: Although RNF213 p.R4810K, a genetic susceptibility variant for moyamoya disease (MMD), is associated with intracranial artery stenosis/occlusion (ICASO), the impact of this variant on ischemic stroke patients in non-young adults is unclear. We aimed to determine the characteristics of non-young adult stroke patients with RNF213 p.R4810K., Methods: We retrospectively identified acute ischemic stroke patients ≥50 years who were admitted to our hospital and underwent intracranial vascular imaging. We reviewed the patients with RNF213 p.R4810K and compared stroke characteristics and the frequency and location of ICASO between patients with and without the variant., Results: Among 341 patients, RNF213 p.R4810K was identified in 7 patients (2.1%). Five of the 7 patients with the variant (71%) had multiple ICASO without any finding of MMD and remaining 2 patients had no ICASO. The presumed etiologies of ICASO were atherosclerosis in 3 cases, vasculitis in 1, and undetermined vasculopathy in 1. ICASO in the anterior circulation was more common in patients with the variant than in those without (71% vs. 25%). The internal carotid artery, the M1 segment of the middle cerebral artery, the A1 segment of the anterior cerebral artery, and the P1 segment of the posterior cerebral artery, which were the most frequently affected arteries in MMD, were more often affected in the variant group., Conclusions: Non-young adult stroke patients with RNF213 p.R4810K are more likely to have ICASO in arterial segments commonly affected in MMD. The etiology of their ICASO exhibited diverse mechanisms, possibly depending on vascular risk and other environmental factors., (Copyright © 2023. Published by Elsevier B.V.)

Dynamic behavior of intermediate adsorbates, such as diffusion, spillover, and reverse spillover, has a strong influence on the catalytic performance in oxide-supported metal catalysts. However, it is challenging to elucidate how the intermediate adsorbates move on the catalyst surface and find active sites to give the corresponding products. In this study, the effect of the dynamic behavior of methoxy intermediate on methanol decomposition on a Pt/TiO 2 (110) surface has been clarified by combination of scanning tunneling microscopy (STM), temperature-programmed desorption (TPD), and density functional theory (DFT) calculations. The methoxy intermediates were formed by the dissociative adsorption of methanol molecules on Pt nanoparticles at room temperature followed by spillover to the TiO 2 (110) support surface. TPD results showed that the methoxy intermediates were thermally decomposed at >350 K on the Pt sites to produce CO (dehydrogenation) and CH 4 (C-O bond scission). A decrease of the Pt nanoparticle density lowered the activity for the decomposition reaction and increased the selectivity toward CH 4 , which indicates that the reaction is controlled by diffusion and reverse spillover of the methoxy intermediates. Time-lapse STM imaging and DFT calculations revealed that the methoxy intermediates migrate on the five-fold coordinated Ti (Ti 5c ) sites along the [001] or [ 1 1 ¯ 0 ] direction with the aid of hydrogen adatoms bonded to the bridging oxygens (O br ) and can move over the entire surface to seek and find active Pt sites. This work offers an in-depth understanding of the important role of intermediate adsorbate migration in the control of the catalytic performance in oxide-supported metal catalysts.

Short-pulse laser is popular for its advantages like less pain. However, its effectiveness is still debated. The aim of this study was to compare fundus autofluorescence (FAF) luminosity changes of laser photocoagulation scars between the conventional laser (0.2 s) and the short-pulse laser (0.02 s) for diabetic retinopathy. Conventional and short-pulse laser photocoagulations were performed in six and seven eyes, respectively. FAF images were captured at 1, 3, 6, 12, and 18 months after the treatments. To evaluate FAF, individual gray-scale values of the laser scars adjacent to the retinal arcade vessels were recorded; then, the mean gray values of the scars were divided by the luminosity of arcade vein. The average luminosity ratio of laser scars at 1, 3, 6, 12, and 18 months were 1.51 ± 0.17, 1.26 ± 0.07, 1.21 ± 0.03, 0.95 ± 0.11, and 0.89 ± 0.05 with conventional laser and 1.91 ± 0.13, 1.50 ± 0.15, 1.26 ± 0.08, 1.18 ± 0.06, and 0.97 ± 0.04 with short-pulse laser, respectively. Findings suggest the short-pulse laser displayed delayed hypoautofluorescence progression. This implies potential postponement in post-irradiation atrophic changes, as well as metabolic amelioration delay in the ischemic retina, when compared to conventional laser treatment.

Purpose: Little is known about whether pre-hospital advanced airway management (AAM) under the presence of a physician could improve outcome of patients with cardiac arrest, compared with pre-hospital AAM under the absence of a physician., Methods: This retrospective multicentre-cohort study enrolled consecutive patients who were transported to participating hospitals after out-of-hospital cardiac arrest in Japan between 1 June 2014 and 31 December 2019. We included patients who underwent pre-hospital AAM and resuscitation after arrival at hospital, and who were ≥18 years of age, with medical aetiologies. The primary outcome was favourable neurological survival (Cerebral Performance Category score of 1 or 2) one month after cardiac arrest. The primary outcome was called one-month favourable neurological survival. The first confirmed cardiac rhythm was defined using 3-lead electrocardiogram monitor or an automated external defibrillator and by determining whether the carotid artery was pulsating. Previous research found that the presence of a pre-hospital physician was associated with improved patients' outcomes, after the type of first confirmed cardiac rhythm was considered. Therefore, the first confirmed cardiac rhythm in current study was subdivided into non-shockable or shockable groups. A multivariable logistic regression analysis was performed on propensity score-matched patients., Results: We analysed 16,703 patients. Among the 2,346 patients in the non-shockable group, 1.2% ( N  = 29) achieved the primary outcome. The adjusted odds ratio of pre-hospital AAM with or without a physician for the primary outcome in the results of the non-shockable group was 4.64 (95% confidence interval: 1.81-14.4). Among the 826 patients in the shockable group, 16.9% ( N  = 140) achieved the primary outcome and the adjusted odds ratio of pre-hospital AAM with or without a physician for the primary outcome in the results of the shockable group was 1.05 (95% confidence interval: 0.67-1.63)., Conclusions: This retrospective multicentre-cohort study found that pre-hospital AAM under the presence of a physician was significantly associated with increased neurological outcome in specific patients with cardiac arrest, compared with pre-hospital AAM under the absence of a physician., 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., (© 2023 The Author(s).)

Various transition metal catalysts have been utilized for ethylene polymerization. Silver catalysts have attracted less attention as the catalysts, but are potential for production of high molecular weight polyethylene. Herein, we report that silver complexes with various N -heterocyclic carbene (NHC) ligands in combination with modified methylaluminoxane (MMAO) afford polyethylene with high molecular weight (melting point over 140°C). SEM observation showed that the produced polyethylene has ultra-high molecular weight. NMR investigation of the reaction between the silver complexes with organoaluminums indicate that the NHC ligands transfer from the silver complex to aluminum to produce NHC aluminum complexes. Ph 3 C[B(C 6 F 5 ) 4 ] abstract methyl group from the NHC aluminum complex to afford cationic aluminum complex. The NHC aluminum complex promoted ethylene polymerization in the presence of Ph 3 C[B(C 6 F 5 ) 4 ] and organoaluminums. NHC ligand also promoted ethylene polymerization in combination with MMAO to produce polyethylene with high melting point (140.7°C). Thus, the aluminum complexes are considered to be the actual active species in silver-catalyzed ethylene polymerization., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

CXCL12, belonging to the CXC chemokine family, is a weak agonist of platelet aggregation. We previously reported that the combination of CXCL12 and collagen at low doses synergistically activates platelets via not CXCR7 but CXCR4, a specific receptor for CXCL12 on the plasma membrane. Recently, we reported that not Rho/Rho kinase, but Rac is involved in the platelet aggregation induced by this combination. Ristocetin is an activator of the von Willebrand factor that interacts with glycoprotein (GP) Ib/IX/V, which generates thromboxane A2 via phospholipase A2 activation, resulting in the release of the soluble CD40 ligand (sCD40L) from human platelets. In the present study, we investigated the effects of a combination of ristocetin and CXCL12 at low doses on human platelet activation and its underlying mechanisms. Simultaneous stimulation with ristocetin and CXCL12 at subthreshold doses synergistically induce platelet aggregation. A monoclonal antibody against not CXCR7 but CXCR4 suppressed platelet aggregation induced by the combination of ristocetin and CXCL12 at low doses. This combination induces a transient increase in the levels of both GTP-binding Rho and Rac, followed by an increase in phosphorylated cofilin. The ristocetin and CXCL12-induced platelet aggregation as well as the sCD40L release were remarkably enhanced by Y27362, an inhibitor of Rho-kinase, but reduced by NSC23766, an inhibitor of the Rac-guanine nucleotide exchange factor interaction. These results strongly suggest that the combination of ristocetin and CXCL12 at low doses synergistically induces human platelet activation via Rac and that this activation is negatively regulated by the simultaneous activation of Rho/Rho-kinase.

The Delta-Notch system plays a vital role in many areas of biology and typically forms a salt and pepper pattern in which cells strongly expressing Delta and cells strongly expressing Notch are alternately aligned via lateral inhibition. In this study, we consider cell rearrangement events, such as cell mixing and proliferation, that alter the spatial structure itself and affect the pattern dynamics. We model cell rearrangement events by a Poisson process and analyze the model while preserving the discrete properties of the spatial structure. We investigate the effects of the intermittent perturbations arising from these cell rearrangement events on the discrete spatial structure itself in the context of pattern formation and by using an analytical approach, coupled with numerical simulation. We find that the homogeneous expression pattern is stabilized if the frequency of cell rearrangement events is sufficiently large. We analytically obtain the balanced frequencies of the cell rearrangement events where the decrease of the pattern amplitude, as a result of cell rearrangement, is balanced by the increase in amplitude due to the Delta-Notch interaction dynamics. Our framework, while applied here to the specific case of the Delta-Notch system, is applicable more widely to other pattern formation mechanisms.

Background: Drug-induced hypersensitivity syndrome (DIHS), including Stevens-Johnson syndrome (SJS), is a severe rash that often develops 2-6 weeks after the intake of the causative drug; however, its diagnosis is sometimes difficult. This article describes a case in which a patient with DIHS-induced multiple organ failure was successfully treated with blood purification therapy., Case Presentation: A male patient in his 60s was admitted to our hospital with autoimmune encephalitis. The patient was treated with steroid pulse therapy, acyclovir, levetiracetam, and phenytoin. From the 25th day, he presented with fever (≥ 38 °C) as well as miliary-sized erythema on the extremities and trunk, followed by erosions. DIHS and SJS were suspected; accordingly, levetiracetam, phenytoin, and acyclovir were discontinued. On the 30th day, his condition further deteriorated, and he was admitted to the intensive care unit for ventilatory management. The next day, he developed multi-organ failure and was started on hemodiafiltration (HDF) for acute kidney injury. Although he presented with hepatic dysfunction and the appearance of atypical lymphocytes, he did not meet the diagnostic criteria for DIHS or SJS/toxic epidermal necrolysis. Therefore, he was diagnosed with multi-organ failure caused by severe drug eruption and underwent a 3-day treatment with plasma exchange (PE) in addition to HDF. Accordingly, the patient was diagnosed with atypical DIHS. After being started on blood purification therapy, the skin rash began to disappear; moreover, the organ damage improved, with a gradual increase in urine output. Eventually, the patient was weaned off the ventilator and transferred to the hospital on the 101st day., Conclusions: HDF + PE could effectively treat multi-organ failure caused by atypical DIHS, which is difficult to diagnose., (© 2023. The Author(s).)

Difficulties in immediately distinguishing Stenotrophomonas maltophilia (SM) bacteremia from Pseudomonas aeruginosa (PA) bacteremia in the clinical setting can lead to treatment delay. We aimed to develop a scoring system to immediately distinguish SM bacteremia from PA bacteremia using clinical indicators. We enrolled cases of SM and PA bacteremia in adult patients with hematological malignancies between January 2011 and June 2018. The patients were randomized into derivation and validation cohorts (2:1), and a clinical prediction tool for SM bacteremia was developed and verified. In total, 88 SM and 85 PA bacteremia cases were identified. In the derivation cohort, the following independent predictors of SM bacteremia were identified: no evidence of PA colonization, antipseudomonal β-lactam breakthrough bacteremia, and central venous catheter insertion. We scored each of the three predictors according to their regression coefficient (2, 2, and 1, respectively). Receiver operating characteristic curve analysis confirmed the score's predictive performance, with an area under the curve of 0.805. The combined sensitivity and specificity (0.655 and 0.821) was highest with a cut-off value of 4 points. Positive and negative predictive values were 79.2% (19/24) and 69.7% (23/33), respectively. This novel predictive scoring system is potentially useful for distinguishing SM bacteremia from PA bacteremia, which would facilitate immediate administration of appropriate antimicrobial therapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Snow sports are a popular recreational activity; however, the incidence of injury of snow sports can be high for skiers and snowboarders. Our hospital receives severe trauma cases from snow resorts and hospitals throughout the region. This study aimed to determine whether the risk of snow sports-related major trauma that requires emergency surgery under general anesthesia varies by the equipment and injury mechanism., Methods: This retrospective cohort study included patients with snow sports trauma referred to Gifu University Hospital, Japan between November 2010 and March 2020. We analyzed the need for emergency operation under general anesthesia within 24 h using Fisher's exact test. We identified 106 patients: (1) 90 in the snowboarders' group and 16 in the skiers' group or (2) 46 in the fall after jumping group (jumping group), 27 in the collide with other people and obstacle group (collision group), and 33 in the fall during gliding group (gliding group)., Results: Snowboarders were nearly twice as likely as skiers to require emergency surgery under general anesthesia (44% vs. 25%; p = 0.236]. No significant associations were found between emergency surgery under general anesthesia and injury mechanism, but half of the patients in the jumping group required emergency surgery., Conclusions: Snowboard as equipment and falls after jumping as a mechanism of injury tended to be associated with emergency surgery under general anesthesia, with no significant differences. In order to provide adequate resources for snow sports trauma, the cause of the patient's injury is strongly related to the urgency of the condition, and transport to a trauma center should be actively considered. Further studies are warranted with respect to the effects of personal protective equipment and skill level., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022. Published by Elsevier Ltd.)