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Purpose: In DRLs 2020, the entrance surface air kerma (Ka,e) was set to 17 mGy/min as the reference dose rate in fluoroscopy. But, Ka,e in fluoroscopy for different regions and Ka,e in exposure was not set. A multicenter survey was conducted to evaluate Ka,e by each area., Methods: Ka,e for each area was analyzed for 79 facilities attending this survey (274 machines and 461 protocols). When the protocols were changed by the difference in disease, angiography, or IVR, the difference rate of Ka,e was evaluated. Ka,e before and after modifying the incident air kerma at the patient entrance reference point (Ka,r) and air kerma area product (P KA ) difference rate were calculated when protocols were changed, considering the DRLs 2020., Results: There were dose differences in Ka,e by each area. Compared to DRLs 2020, 36 protocols from 13 facilities modified their protocols, all of which reduced Ka,e., Conclusion: Although reducing Ka,e does not necessarily reduce Ka,r, and P KA , comparison of Ka,e by each area is expected to optimize medical exposure protection, including evaluation of quality control.

Background: Carotid artery dissection is a common cause of ischemic stroke, predominantly affecting the internal carotid artery, with rare involvement of the common carotid artery (CCA). The limited literature makes diagnosis and management challenging, particularly in asymptomatic patients. In this report, the authors present a unique case of spontaneous, asymptomatic CCA dissection that resembled a carotid web, shedding light on its clinical spectrum and management., Observations: A 70-year-old man was diagnosed with an intimal flap in the left CCA. Although the findings resembled those of a carotid web, cerebral angiography confirmed the presence of an intimal flap and arterial wall irregularities indicative of vascular dissection. Endarterectomy successfully prevented the stroke, and the postoperative recovery was uneventful. Pathological examination confirmed the diagnosis of CCA dissection., Lessons: Spontaneous CCA dissection, though rare, presents significant diagnostic and therapeutic challenges. Because of morphological similarities, differentiating the diagnosis from a carotid web can be difficult. Available treatment strategies include antiplatelet therapy and surgical intervention. In this case, endarterectomy was chosen to avoid antithrombic treatment in anticipation of further invasive treatments for other conditions. The successful outcome highlights the potential as a treatment option, emphasizing the need for an individualized approach to each patient. https://thejns.org/doi/10.3171/CASE24344.

The recurrence of chronic subdural hematoma (CSDH) after surgical treatment is a severe problem with no effective prevention method. This retrospective study aimed to investigate factors associated with CSDH recurrence after burr hole surgery and hematoma changes on computed tomography before surgery to examine prevention methods for recurrence. A total of 166 hematomas were enrolled in this study, with 139 patients undergoing burr hole surgery for CSDH. Among these patients, 17 (12 %) had recurrence. Propensity score matching was performed based on postoperative drug therapy, including goreisan, carbazochrome sodium sulfonate hydrate, and tranexamic aid, resulting in 39 matched cases in 0-2 and 3 drug therapy groups. The recurrence rates were 18 % for the 0-2-drug therapy group and 3 % for the 3-drug therapy group. Univariate analysis revealed that the use of 0-2 drugs was associated with a higher risk of CSDH recurrence (odds ratio [OR], 8.31; 95 % confidence interval [CI], 0.97-71.17; p = 0.05) compared to the use of 3 drugs. Multivariate regression analysis further confirmed that 0-2 drug therapy after surgery was associated with an increased risk of CSDH recurrence (OR, 11.06; 95 % CI, 1.16-105.4; p = 0.037). Additionally, 36 hematomas were evaluated before surgery, with hematoma changes such as lower density and new trabecular formation detected in 14 CSDHs (39 %). Multivariate regression analysis showed that 3-drug therapy was associated with more cases of hematoma change than 0-2-drug therapy (OR, 13.9; 95 % CI, 1.09-177.65; p = 0.043). The 3-drug therapy was effective in reducing the recurrence of hematoma after burr hole surgery and promoted hematoma thrombosis., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Techniques for triggering neural differentiation of embryonic and induced pluripotent stem cells into neural stem cells and neurons have been established. However, neural induction of mesenchymal stem cells, including dental pulp stem cells (DPSCs), has been assessed primarily based on neural-related gene regulation, and detailed studies into the characteristics and differentiation status of cells are lacking. Therefore, this study was aimed at evaluating the cellular components and differentiation pathways of neural lineage cells obtained via neural induction of human DPSCs. Human DPSCs were induced to neural cells in monolayer culture and examined for gene expression and mechanisms underlying differentiation using microarray-based ingenuity pathway analysis. In addition, the neural lineage cells were subjected to single-cell RNA sequencing (scRNA-seq) to classify cell populations based on gene expression profiles and to elucidate their differentiation pathways. Ingenuity pathway analysis revealed that genes exhibiting marked overexpression, post-neuronal induction, such as FABP7 and ZIC1, were associated with neurogenesis. Furthermore, in canonical pathway analysis, axon guidance signals demonstrated maximum activation. The scRNA-seq and cell type annotations revealed the presence of neural progenitor cells, astrocytes, neurons, and a small number of non-neural lineage cells. Moreover, trajectory and pseudotime analyses demonstrated that the neural progenitor cells initially engendered neurons, which subsequently differentiated into astrocytes. This result indicates that the aforementioned neural induction strategy generated neural stem/progenitor cells from DPSCs, which might differentiate and proliferate to constitute neural lineage cells. Therefore, neural induction of DPSCs may present an alternative approach to pluripotent stem cell-based therapeutic interventions for nervous system disorders., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Histopathologic examinations of primary central nervous system lymphoma (PCNSL) reveal concentric accumulation of lymphocytes in the perivascular area with fibrosis. However, the nature of this fibrosis in "stiff" PCNSL remains unclear. We have encountered some PCNSLs with hard masses as surgical findings. This study investigated the dense fibrous status and tumor microenvironment of PCNSLs with or without stiffness. We evaluated by silver-impregnation nine PCNSLs with stiffness and 26 PCNSLs without stiffness. Six of the nine stiff PCNSLs showed pathological features of prominent fibrosis characterized by aggregation of reticulin fibers, and collagen accumulations. Alpha-smooth muscle actin (αSMA)-positive spindle cells as a cancer-associated fibroblast, the populations of T lymphocytes, and macrophages were compared between fibrous and control PCNSLs. Fibrous PCNSLs included abundant αSMA-positive cells in both intra- and extra-tumor environments (5/6, 87% and 3/6, 50%, respectively). Conversely, only one out of the seven control PCNSL contained αSMA-positive cells in the intra-tumoral area. Furthermore, the presence of extra-tumoral αSMA-positive cells was associated with infiltration of T lymphocytes and macrophages. In conclusion, recognizing the presence of dense fibrosis in PCNSL can provide insights into the tumor microenvironment. These results may help stratify patients with PCNSL and improve immunotherapies for these patients., (© 2024. The Author(s).)

Magnetic resonance imaging (MRI) is an indispensable tool in neurosurgery, though it sometimes faces challenges such as "tumor mimicry." While intraoperative MRI (iMRI) is widely recognized for its usefulness in achieving maximal safe resection during glioma surgery, instances of tumor mimicry still occur on iMRI. Moreover, reports on tumor mimics observed through iMRI, particularly in low-grade gliomas, remain scarce. In this article, we present a case of oligodendroglioma, where a newly emerged T2 high-signal intensity region on iMRI necessitated differentiation from tumor expansion. A 23-year-old man presented with a newly diagnosed brain tumor and underwent surgical removal. An iMRI taken after tumor removal revealed a newly emerged T2 hyperintense area without diffusion restriction around the resection cavity, which was not observed in the preoperative MRI. Suspecting residual tumor, we performed additional resection. An MRI on the following day confirmed that the T2 hyperintense area identified on the iMRI had been completely resected but also revealed an enlarged T2 high-signal area over a wider region. Histopathology found no tumor cells in the additionally resected area, indicating that the iMRI finding was a tumor mimic. Six months later, the T2 high-signal area around the resection cavity had disappeared on MRI without any additional treatment. This case highlights the challenge of distinguishing between T2 hyperintense mimicry and tumor enlargement during glioma surgery seen on iMRI. Despite the significant value of iMRI, our report underscores the need for careful interpretation in neurosurgical practice, particularly with non-contrast-enhancing tumors., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Neurofibromatosis type 1 (NF-1) is often characterized by vascular disorders related to vessel vulnerability that can lead to unfavorable outcomes. Here, we describe a case of NF-1 complicated with a massive subcutaneous hematoma posing a risk of visual impairment for which rapid decompression and a subsequent less invasive approach result in a favorable outcome., Case Description: A 40-year-old woman with NF-1 presented with a massive left subcutaneous temporal hematoma following a mild head contusion. Four days after hospitalization, the hematoma increased in size and severely compressed the left eye, prompting immediate hematoma removal to preserve visual function. Immediately after the hematoma removal, a superficial temporal arteriovenous fistula was found on the digital subtraction angiography and embolized by the endovascular procedure. Her visual acuity was preserved, and no bleeding recurrence was observed throughout the follow-up., Conclusion: Surgical hematoma removal followed by endovascular treatment was effective in preserving visual function. Since vessel fragility is characteristic of patients with NF-1, it should be kept in mind that vascular complications may lead to serious clinical outcomes. In certain NF-1 cases, less invasive treatments for vascular abnormalities may be preferable., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Background: Intraoperative photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is a widely adopted technique to enhance the extent of resection during high-grade glioma (HGG) surgery. Recent updates to the package insert for 5-ALA in Japan now allow its use in combination with drugs that may induce photosensitivity, such as talaporfin sodium (TS). TS is employed in intraoperative photodynamic therapy (PDT) and has been shown to improve overall survival. The combination of 5-ALA with TS is expected to offer further benefits. However, the safety of this combination had not been established. This study reports on the safety of 5-ALA-PDD with TS-PDT in the treatment of recurrent HGG., Methods: 7 patients with recurrent HGG underwent tumor resection using a combination of 5-ALA-PDD and TS-PDT. The incidence of photosensitivity as an adverse effect associated with 5-ALA and TS was evaluated as described in the package insert. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0., Results: Tumor-specific fluorescence intensity was strong in 4 cases and weak in 3. Photosensitivity occurred in only 1 patient (14.3%). Three patients exhibited CTCAE grade 1 or 2 abnormal liver function, and 1 patient experienced CTCAE grade 1 γ-GTP elevation. All abnormalities improved during follow-up., Conclusions: The combined use of 5-ALA-PDD and TS-PDT for HGG surgery did not increase the risk of serious adverse events in our study. Further investigations with a larger number of cases are needed for a more accurate assessment of its safety and efficacy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to evaluate the refractive error in patients undergoing combined phacovitrectomy with and without gas tamponade., Methods: This was a retrospective chart review including patients undergoing phacoemulsification alone (Group 1), combined phacovitrectomy for epiretinal membrane (Group 2), and combined phacovitrectomy with gas tamponade for rhegmatogenous retinal detachment (RRD) (Group 3). Axial length and keratometry were measured using an optical biometric system (Argos, Alcon Laboratories. Inc.), and a three-piece intraocular lens (IOL; NX-70S) was implanted in all groups. In each group, the prediction error at 3 months was calculated using IOL power calculation formulas (SRK/T, Hill-RBF, Kane, and Barrett Universal II) for each eye. Outcome measures included the mean prediction error (MPE), its standard deviation (SD), and the mean absolute error (MAE). The change in IOL position at 3 months was also assessed using anterior segment optical coherence tomography., Results: A total of 104 eyes were included (Group 1: 30; Group 2: 34; Group 3: 40 eyes). The MPE was -0.08 ± 0.37 diopters (D), -0.26 ± 0.32 D, and -0.59 ± 0.34 D in Group 1, Group 2, and Group 3, respectively, using the Barrett Universal II formula (P < 0.01, ANOVA). The movement forward in the IOL position was 0.95 ± 0.16 mm, 0.94 ± 0.12 mm, and 1.07 ± 0.20 mm in Group 1, Group 2, and Group 3, respectively (P < 0.01). No significant difference was shown in MPE among the four formulas after combined phacovitrectomy with gas (P = 0.531)., Conclusions: Phacovitrectomy in RRD induced a significant myopic shift using any of the clinically available formulas. This suggests that myopic shift should be taken into consideration for better refractive outcomes in phacovitrectomy with gas tamponade in RRD., (© 2024. The Author(s).)

Background: Antitumor necrosis factor (TNF)-α antibodies have improved the outcome of inflammatory bowel disease (IBD); but half of patients remain unresponsive to treatment. Interleukin-18 (IL-18) gene polymorphism is associated with resistance to anti-TNF-α antibodies, but therapies targeting IL-18 have not been clinically applied. Only the mature protein is biologically active, and we aimed to investigate whether specific inhibition of mature IL-18 using a monoclonal antibody (mAb) against a neoepitope of caspase-cleaved mature IL-18 could be an innovative treatment for IBD., Methods: The expression of precursor and mature IL-18 in patients with UC was examined. Colitis was induced in C57/BL6 mice by administering dextran sulfate sodium (DSS), followed by injection with anti-IL-18 neoepitope mAb. Colon tissues were collected and subjected to histological analysis, immunohistochemistry, immunoblotting, and quantitative polymerase chain reaction. Colon epithelial permeability and microbiota composition were analyzed., Results: Mature IL-18 expression was elevated in colon tissues of patients with active ulcerative colitis. Administration of anti-IL-18 neoepitope mAb ameliorated acute and chronic DSS-induced colitis; reduced interferon-γ, TNF-α, and chemokine (CXC motif) ligand-2 production and epithelial cell permeability; promoted goblet cell function; and altered the intestinal microbiome composition. The suppressive effect of anti-IL-18 neoepitope mAb was superior to that of anti-whole IL-18 mAb. Furthermore, combination therapy with anti-TNF-α Ab suppressed acute and chronic colitis additively by suppressing cytokine expressions and reducing cell permeability by upregulating claudin1 and occludin expression., Conclusions: Anti-IL-18 neoepitope mAb ameliorates acute and chronic colitis, suggesting that this mAb will be an innovative therapeutic option for IBD., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Recently, the detection of superficial non-ampullary duodenal epithelial tumors (SNADETs) including adenomas and superficial duodenal carcinomas has increased. Various endoscopic treatment methods have also been reported for SNADETs, but there are few reports on the natural history. The aim of this study was to analyze factors related to tumor growth and determine the characteristics of SNADETs which need early therapeutic intervention., Methods: A single-center, retrospective study was performed on the medical records of 309 patients with SNADETs who underwent endoscopic or surgical resection between January 2010 and May 2021. Of these, 41 patients who were followed up for more than 1 year by endoscopy were analyzed. The primary outcome was an analysis of the tumor growth speed. Secondary outcomes were the relationship between the tumor growth speed and mucin phenotype, tumor size and findings of magnifying endoscopy with narrow-band imaging (M-NBI)., Results: The observation period was 24 months (13-182). Tumor growth speed was 1.1 mm/year (0-21.6). Tumor diameter ≥10 mm at first detection (p = 0.004; odds ratio 19.5 [2.03-186.96]) and mixed type by M-NBI (p = 0.036; odds ratio 9.69 [1.05-89.88]) were identified as risk factors of tumors growing at a rate of ≥3 mm/year. There was no statistically significant difference in the speed of tumor growth between the different mucin immunohistochemical phenotypes., Conclusion: Initial tumor size and findings of M-NBI are useful to predict tumor growth and consider early intervention., (© 2024 S. Karger AG, Basel.)

Background: Treatment outcome data of stereotactic radiosurgery (SRS) for vestibular schwannomas (VS) in patients ≥75 years (late elderly) are lacking. Approximately 39% of patients ≥75 years with VS were reported to experience severe facial palsy after surgical removal. This study compared the treatment outcomes post-SRS for VS between patients ≥75 and 65-74 years (early elderly)., Methods: Of 453 patients who underwent gamma knife SRS for VS, 156 were ≥65 years old. The late and early elderly groups comprised 35 and 121 patients, respectively. The median tumor volume was 4.4 cc, and the median radiation dose was 12.0 Gy., Results: The median follow-up periods were 37 and 56 months in the late and early elderly groups, respectively. Tumor volume control was observed in 27 (88%) and 95 (83%) patients ( P = 0.78), while additional procedures were required in 2 (6%) and 6 (6%) patients ( P = 1.00) in the late and early elderly groups, respectively. At the 60 th and 120 th months post-SRS, the cumulative tumor control rates were 87%, 75%, 85%, and 73% ( P = 0.81), while the cumulative clinical control rates were 93% and 87%, 95%, and 89% ( P = 0.80), in the late and early elderly groups, respectively. In the early elderly group, two patients experienced facial pain, and one experienced facial palsy post-SRS; there were no adverse effects in the late elderly group (both P = 1.00)., Conclusion: SRS is effective for VS and beneficial in patients ≥75 years old as it preserves the facial nerve., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Introduction: Inflammation in ulcerative colitis (UC) originates in the colorectal mucosa. Transcriptome sequencing analysis of the colorectal mucosa allows the identification of potential neuropeptides related to local neurotransmission. The intestinal mucus lining the surface of the mucosa may harbor biomarkers of mucosal inflammation; however, this has not been sufficiently investigated, given the difficulty in obtaining human samples. We previously reported the feasibility of obtaining mucin samples for proteomic analysis by brushing during colonoscopy. Herein, we aimed to investigate the composition of the intestinal mucus and detect neuropeptides characteristic of UC., Methods: Mucus and mucosal samples were collected from patients with UC from the colorectum in areas showing remission or active UC using a brush catheter and biopsy forceps during colonoscopy. RNA sequencing findings of mucus samples of active and remission areas were compared. RNA and protein expression levels of significantly upregulated neuropeptides were analyzed., Results: Of the neuropeptides associated with UC, somatostatin (SST) was significantly elevated in areas of remission, according to RNA sequencing results of mucus and expression levels in mucus RNA and proteins. Conversely, SST expression in the mucosa was increased in the inflamed areas. Flow cytometry revealed that the fluorescence intensity of SST-positive cells in the remission zone was higher in the mucus than in the mucosa., Conclusion: SST expression in the mucus is considered to be an important factor associated with UC activity., (© 2024 S. Karger AG, Basel.)

Background  Symptomatic cerebellar cyst formation after surgery is rare and the mechanism remains unknown. We describe a cerebellar cyst that gradually expanded, becoming symptomatic, after the removal of a foramen magnum meningioma and discuss the mechanism of cyst formation. Case Description  A 76-year-old woman with a tumor at the foramen magnum was treated by posterior fossa craniotomy and C1 hemilaminectomy. The patient suddenly developed cerebellar symptoms and consciousness disturbance approximately 1 week into an otherwise good postoperative course. Imaging showed a subcutaneous pseudomeningocele in the occipital region and cerebellar cyst formation. After resolution by fenestration of the cerebellar cyst and duraplasty, the patient's symptoms gradually improved. No tumor or cerebellar cyst recurrence has been detected in over 5 years since the surgery. Conclusion  Postoperative pseudomeningocele appeared crucial for cerebellar cyst formation. Postoperative development of symptomatic cerebellar cysts is rare but should be recognized as a serious, sometimes life-threatening, postoperative complication of posterior fossa surgery., Competing Interests: Conflict of Interest None declared, (Asian Congress of Neurological Surgeons. 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/ ).)

Background: Neurenteric cysts are relatively rare benign congenital intracranial cystic lesions that enlarge rarely and very slowly. The authors present a case of an enlarging neurenteric cyst at the craniocervical junction with a fluid-fluid level on magnetic resonance imaging (MRI)., Observations: A 34-year-old man with no significant medical history underwent head MRI to investigate mild headaches. An incidental cystic lesion, approximately 8 mm in diameter, was revealed at the craniocervical junction. Serial follow-up MRI showed cyst enlargement with a fluid-fluid level. Four years later, the cyst reached a size of 15 mm and was surgically removed. The cyst contained cloudy fluid with a high protein concentration, without any bleeding or tissue fragments. Pathological examination confirmed the diagnosis of a neurenteric cyst. The patient recovered well, was discharged home, and has remained recurrence free for 2 years., Lessons: The growth dynamics of the relatively rapidly expanding neurenteric cyst at the craniocervical junction were monitored over time using MRI. This cyst exhibited the distinctive feature of a fluid-fluid level as it enlarged. Investigating the mechanisms underlying fluid-fluid level formation may offer novel insights into the pathogenesis of cyst enlargement. https://thejns.org/doi/10.3171/CASE24180.

We report a simple and atom-efficient method for the synthesis of bithiophene-fused isoquinolines by iridium-catalyzed [2 + 2 + 2] cycloaddition of bithiophene-linked diynes with nitriles. All three structural isomers of bithiophene-linked diynes underwent [2 + 2 + 2] cycloaddition, and the trend in the reactivity for cycloaddition was diyne 1 = diyne 3 > diyne 2 . Dibenzothiophene-linked diyne also reacted with nitriles to form a variety of cycloadducts. Cycloaddition of bithiophene-linked diynes with alkynes and an isocyanate formed naphthodithiophenes and a 2-pyridone derivative, respectively. Cycloadducts bearing a 2-aminopyridine moiety and benzothiophene rings showed intense fluorescence at around 530 nm and gave a fluorescence quantum yield of 0.44. Furthermore, quantum chemical calculations provided insight into the origin of the difference in reactivity of three bithiophene-linked diynes. The different reactivities of the three diynes 1-3 are believed to originate from the step where an iridacyclopentadiene reacts with a coordinated nitrile to form azairidabicyclo[3.2.0]heptatriene. HOMOs of iridacyclopentadiene play a decisive role in this step.

Background: Numerous biological interventions and small molecules are used to treat Crohn's disease; however, the effectiveness of these treatments varies largely. Non-responsiveness to biological therapies is associated with interleukin (IL)-18 gene polymorphisms and high IL-18 expression has been implicated in the pathogenesis of Crohn's disease., Aims: The aim of this study was to elucidate the expression of precursor and mature IL-18 in patients with Crohn's disease who exhibited varied responses to cytokine-targeted treatments and determine whether selective inhibition of mature IL-18 offers a novel therapeutic avenue., Methods: We generated a monoclonal antibody that specifically recognizes the neoepitope of caspase-cleaved mature IL-18. Expression of precursor and mature IL-18 was analyzed in patients with Crohn's disease. Anti-mature IL-18 monoclonal antibodies were intraperitoneally administered in an acute colitis mouse model, and the disease activity index, body weight loss, tissue pathology, proinflammatory cytokine expression, goblet cell function, and microbiota composition were assessed., Results: Precursor and mature IL-18 expression was upregulated and goblet cell function was impaired in patients with Crohn's disease who were unresponsive to biological therapies. Administration of anti-mature IL-18 antibodies ameliorated induced colitis by repairing goblet cell function and restoring the mucus layer., Conclusions: The newly developed monoclonal antibody holds promise as a therapeutic alternative for Crohn's disease., (© 2024. The Author(s).)

Background:  The effects of sleep deprivation on surgical performance have been well documented. However, reports on the effects of sleep deprivation on microneurosurgery are limited. This study aimed to investigate the effects of sleep deprivation on microneurosurgery., Methods:  Ten neurosurgeons participated in the anastomosis of a vessel model using a microscope in sleep-deprived and normal states. We evaluated the procedure time (PT), stitch time (ST), interval time (IT), number of unachieved movements (NUM), leak rate, and practical scale for anastomosis quality assessment. Each parameter was compared between normal and sleep-deprived states. Subanalyses were performed on the two groups based on PT and NUM under the normal state (proficient and nonproficient groups)., Results:  Although no significant differences were noted in PT, ST, NUM, leak rate, or practical scale, IT was significantly prolonged under sleep deprivation compared with the normal state (mean: 258.8 ± 94.0 vs. 199.3 ± 74.9 seconds; p  = 0.02). IT was significantly prolonged under sleep deprivation in the nonproficient group based on both PT and NUM (PT: 234.2 ± 71.6 vs. 321.2 ± 44.7 seconds, p  = 0.04; NUM: 173.3 ± 73.6 vs. 218.7 ± 97.7; p  = 0.02), whereas no significant difference was observed in the proficient group (PT: 147.0 ± 47.0 vs. 165.3 ± 61.1 seconds, p  = 0.25; NUM: 173.3 ± 73.6 vs. 218.7 ± 97.7; p  = 0.25)., Conclusions:  Although IT was significantly prolonged under sleep deprivation in the nonproficient group, there was no decline in performance skills in either the proficient or nonproficient group. The effect of sleep deprivation may require caution in the nonproficient group, but it is possible that certain microneurosurgical outcomes can be achieved under sleep deprivation., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Appropriate exploratory efficacy data from Phase I trials are vital for subsequent phases. Owing to the uniqueness of brain tumors (BTs), use of different strategies to evaluate efficacy is warranted. We studied exploratory efficacy evaluation in Phase I trials involving BTs., Methods: Using Clarivate's Cortellis ™ , 42 Phase I trials of BT interventions conducted from 2020 to 2022 were analyzed for efficacy endpoints, which were set as primary endpoints (PEs) or secondary endpoints (SEs). Additionally, these metrics were compared in two subgroups: trials including only BTs (Group-A) and those including BTs among mixed solid tumors (Group-B)., Results: Selected studies included a median of 1.5 PEs (range, 1-6) and 5 SEs (range, 0-19). Efficacy endpoints were included as PEs and SEs in 2 (5%) and 31 (78%) trials, respectively. Among the latter 31 trials that included 94 efficacy endpoints, 24, 22, 20, 9, and 8 reflected overall response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and disease control rate (DCR), respectively. ORR for BT was determined using various methods; however, the Response Evaluation Criteria in Solid Tumors (RECIST) was used less frequently in Group-A than in Group-B (p = 0.0039)., Conclusions: Recent Phase I trials included efficacy endpoints as SEs, with ORR, PFS, or OS included in ~ 50% trials and DOR or DCR in ~ 25%. No established criteria exist for imaging evaluation of BTs. Phase I trials involving mixed solid tumor cohorts revealed challenges in designing methods to assess the exploratory efficacy of BTs., (© 2024. The Author(s).)

The pathology of idiopathic intracranial hypertension (IIH), a disease characterized by papillary edema and increased intracranial pressure (IICP), is not yet understood; this disease significantly affects quality of life due to symptoms including vision loss, headache, and pulsatile tinnitus. By contrast, superficial siderosis (SS), a disorder in which hemosiderin is deposited on the surface of the cerebral cortex and cerebellum, potentially causes cerebellar ataxia or hearing loss. So far, no cases of IIH with infratentorial and supratentorial cortical SS have been reported. Herein, we report a case of a 31-year-old woman with obesity who developed this condition. The patient suddenly developed headache and dizziness, had difficulty walking, and subsequently became aware of diplopia. Fundus examination revealed bilateral optic nerve congestive papillae and right eye abducens disturbance. Head magnetic resonance imaging (MRI) showed prominent SS on the cerebellar surface and cerebral cortex. Lumbar puncture revealed IICP of 32 cmH 2 O, consistent with the diagnostic criteria for IIH, and treatment with oral acetazolamide was started; subsequently, the intracranial pressure decreased to 20 cmH 2 O. Her abduction disorder disappeared, and the swelling of the optic papilla improved. She was now able return to her life as a teacher without any sequelae. SS is caused by persistent slight hemorrhage into the subarachnoid space. In this case, both infratentorial and supratentorial cortical superficial SS was observed. Although cases of IIH complicated by SS are rare, it should be kept in mind that a causal relationship between IIH and SS was inferred from our case. Our findings also suggest that cerebrospinal fluid dynamic analysis using MRI is effective in diagnosing IIH and in determining the efficacy of treatment.

Purpose: To identify the countermeasures and current status of disaster power outages in the radiology departments of hospitals., Methods: A web-based questionnaire survey of 600 hospitals nationwide was conducted. The questionnaire survey covered 34 items, including availability of power in the radiology department in the event of a disaster and the impact of power outages on medical equipment in the radiology department., Results: In all, 242 facilities (40.3%) responded to our survey. During power outages, 55.8%-68.2% of facilities were able to use CT, digital radiography, and angiography systems with their private generators. In 28.1%-40.7% of facilities, medical information systems were not available in all laboratories. In addition, power outages caused equipment malfunctions in 81.4% of facilities' radiology departments., Conclusion: We have identified the power supplied by private generators to the radiology department's medical equipment and medical information systems. Many medical equipment have malfunctioned due to power outages. Therefore, drills should be conducted to simulate various situations caused by power outages.

Renal medullary angiitis is characterized by interstitial hemorrhaging in the medulla with neutrophil infiltration. An 81-year-old man presented with a fever, kidney dysfunction, and purpura of the legs, which was diagnosed as leukocytoclastic vasculitis. Proteinase 3 antineutrophil cytoplasmic antibodies were weakly positive. A kidney biopsy showed severe tubulointerstitial hemorrhaging with neutrophilic infiltration in the perivascular areas surrounding the vasa recta in the medulla without crescent formation in the glomeruli. An immunofluorescence analysis was negative, and electron microscopy revealed no immune-dense deposits, ruling out immunoglobulin A vasculitis. Intravenous methylprednisolone for three days and plasma exchange followed by oral prednisolone improved his general condition.

Background: Venous varices in the draining vein of arteriovenous malformations (AVMs) can result in compression symptoms. This condition is extremely rare, and its treatments and long-term outcomes are unresolved. Herein, we describe the treatment of a thrombosed venous varix in a draining vein and review the relevant literature., Patient: The patient presented with progressive right-sided hemiparalysis and aphasia. Magnetic resonance imaging revealed flow void accumulation from the corpus callosum to the left ventricle and a 30-mm mass in the left putamen. The patient underwent targeted transarterial embolization to reduce the blood flow to the venous varix and relieve the neurological symptoms. The patient had recovered completely from the right hemiparesis and aphasia 4 years after treatment, with a modified Rankin Scale score of 0., Conclusion: Targeted transarterial embolization for symptomatic venous varix is a palliative treatment that may improve long-term functional outcomes., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Cancer is one of the leading causes of global mortality, and its incidence is increasing annually. Neutron capture therapy (NCT) is a unique anticancer modality capable of selectively eliminating tumor cells within normal tissues. The development of accelerator-based, clinically mountable neutron sources has stimulated a worldwide search for new, more effective compounds for NCT. We synthesized magnetic iron oxide nanoparticles (NPs) that concurrently incorporate boron and gadolinium, potentially enhancing the effectiveness of NCT. These magnetic nanoparticles underwent sequential modifications through silane polycondensation and allylamine graft polymerization, enabling the creation of functional amino groups on their surface. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and transmission electron microscopy (TEM). ICP-AES measurements indicated that boron (B) content in the NPs reached 3.56 ppm/mg, while gadolinium (Gd) averaged 0.26 ppm/mg. Gadolinium desorption was observed within 4 h, with a peak rate of 61.74%. The biocompatibility of the NPs was confirmed through their relatively low cytotoxicity and sufficient cellular tolerability. Using NPs at non-toxic concentrations, we obtained B accumulation of up to 5.724 × 10 10 atoms per cell, sufficient for successful NCT. Although limited by its content in the NP composition, the Gd amount may also contribute to NCT along with its diagnostic properties. Further development of the NPs is ongoing, focusing on increasing the boron and gadolinium content and creating active tumor targeting.

Introduction: Crohn's disease (CD) induces persistent inflammation throughout the gastrointestinal (GI) tract, potentially resulting in complications such as intestinal stenosis and fistulas, particularly in the small bowel. Small bowel capsule endoscopy (SBCE) is recommended for monitoring CD, especially when GI tract patency is maintained. This study aimed to retrospectively assess patients with CD who underwent SBCE to determine the timing of clinical changes and address the current lack of evidence regarding GI tract patency loss during CD treatment., Methods: Of the 166 consecutive patients who underwent SBCE at our institution, 120 were followed up and included in this study. Forty-six patients were excluded due to colitis type or immediate treatment changes post-SBCE. This study focused on the primary and secondary endpoints, including the cumulative stricture-free rate of the GI tract, emergency hospitalization post-SBCE, and post-SBCE treatment strategies, at the discretion of the attending physicians., Results: Demographic data revealed that the mean age of the study population was 43 years and that there was a male predominance (75%). The median disease duration was 12 years and the mean Crohn's Disease Activity Index was 98. During a 1,486-day observation period, 37% of patients experienced treatment changes. A Lewis score of &gt;264 and perianal lesions were identified as independent risk factors for additional treatment needs. Emergency hospitalization occurred in 6% of patients and GI patency failure in 11%. Female sex and Lewis score&gt;264 were associated with higher risks. GI patency rate declined 2 years after SBCE., Conclusions: For patients who experienced no treatment changes based on SBCE results, it is recommended to undergo SBCE monitoring at intervals of no longer than 2 years., (© 2024 S. Karger AG, Basel.)

In developed countries like Japan, the size of the older population is rapidly increasing. Malignant neoplasms rank as the leading cause of death among the geriatric population of Japan, emphasizing the rising demand for cancer care in this demographic. Older patients, besides facing physical and cognitive challenges, are also affected by their social environment, necessitating tailored interventions. Few case reports have detailed the progress of cancer treatment in nonagenarian patients. This study presents the progress of two very old patients with cancer. The first case, a 95-year-old female with chronic constipation underwent emergency surgery for a cecal tumor. Despite initial improvements, her mobility declined after surgery, leading to institutionalization. Recurrent hospitalizations ensued with complications culminating in her death approximately 20 months after surgery. In the second case, a 94-year-old male, initially declining aggressive treatment for a suspected ileocecal malignancy, later opted for supportive care. Despite stable conditions, he eventually died at home after experiencing progressive weakness, which was approximately 20 months after the initial diagnosis. These cases shed light on the management of elderly patients with ileocecal cancer, illustrating the divergent trajectories between surgical intervention and supportive care. The tumor did not recur in the patient who underwent surgery; however, the independence in performing daily living activities declined significantly. In the case managed with the best-supportive care, progression was slow; however, severe anemia became a concern toward the end of life., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ishikawa et al.)

Background: Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are major genetic polycystic kidney diseases that can progress to end-stage kidney disease (ESKD). Longitudinal data on the clinical characteristics associated with clinical outcomes in polycystic kidney disease (PKD), including the development of ESKD and cardiovascular disease (CVD) are lacking in Japan. To address this unmet need the authors are establishing a novel, web-based, Nationwide Cohort Registry Study-the Japanese Registry of PKD (JRP)., Methods: The JRP is a prospective cohort study for ADPKD (aim to recruit n = 1000 patients), and both a retrospective and prospective study for ARPKD (aim to recruit n = 100). In the prospective registry, patients will be followed-up for 10 years every 6 months and 12 months for patients with ADPKD and ARPKD, respectively. Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on April 1, 2024, with recruitment ending on March 31, 2029. (jRCT 1030230618)., Results: Data to be collected include: baseline data, demographics, diagnostic and genetic information, radiological and laboratory findings, and therapeutic interventions. During follow-up, clinical events such as development of ESKD, hospitalization, occurrence of extra kidney complications including CVD events, and death will be recorded, as well as patient-reported health-related quality of life for patients with ADPKD., Conclusions: The JRP is the first nationwide registry study for patients with ADPKD and ARPKD in Japan, providing researchers with opportunities to advance knowledge and treatments for ADPKD and ARPKD, and to inform disease management and future clinical practice., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) αβ sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as 'sustainers'), but not in 'decliners'. Even before vaccination, S-reactive CD4 + T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic microbes. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers., Competing Interests: XL, EI, YT, JD, SY No competing interests declared, HH, HN Works in the Department of Health Development and Medicine, which is an endowed department supported by AnGes, Daicel, and FunPep, (© 2023, Lu, Hayashi, Ishikawa et al.)

Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of porphyrin is not clear. The authors previously reported that heme carrier protein 1 (HCP1) contributes to the transport of porphyrins; specifically, we showed that the production of cancer-specific reactive oxygen species from mitochondria (mitROS) leads in turn to enhanced HCP1 expression. Indomethacin (IND), a non-steroidal anti-inflammatory drug, increases ROS production by affecting mitochondrial electron transfer system. In the present work, the authors investigated the effect of pretreatment with IND on cancer-specific porphyrin accumulation, using both a glioma cell line and a rat brain tumor model. This work demonstrated that exposure of a rat glioma cell to IND results in increased generation of cancer-specific mitROS and accumulation of HCP1 expression and porphyrin concentration. Additionally, systemic dosing of a brain tumor animal model with IND resulted in elevated cellular accumulation of porphyrin in tumor cell. This is an effect not seen with normal brain tissue. Thus, the administration of IND increases intracellular porphyrin concentrations in tumor cell without exerting harmful effects on normal brain tissue, and increased porphyrin concentration in tumor cell may lead to improved PDT effect., Competing Interests: EI received scholarship funds from Eisai Co., Ltd., (Copyright © 2024 JCBN.)

The indole alkaloid gramine, 3-(dimethylaminomethyl)indole, is a defensive specialized metabolite found in some barley cultivars. In its biosynthetic process, the tryptophan (Trp) side chain is shortened by two carbon atoms to produce 3-(aminomethyl)indole (AMI), which is then methylated by N-methyltransferase (HvNMT) to produce gramine. Although side chain shortening is one of the crucial scaffold formation steps of alkaloids originating from aromatic amino acids, the gene and enzyme involved in the Trp-AMI conversion reactions are unknown. In this study, through RNA-seq analysis, 35 transcripts were shown to correlate with gramine production; among them, an uncharacterized cytochrome P450 (CYP) gene, CYP76M57, and HvNMT were identified as candidate genes for gramine production. Transgenic Arabidopsis thaliana and rice overexpressing CYP and HvNMT accumulate AMI, N-methyl-AMI, and gramine. CYP76M57, heterologously expressed in Pichia pastoris, was able to act on Trp to produce AMI. Furthermore, the amino group nitrogen of Trp was retained during the CYP76M57-catalyzed reaction, indicating that the C 2 shortening of Trp proceeds with an unprecedented biosynthetic process, the removal of the carboxyl group and C α and the rearrangement of the nitrogen atom to C β . In some gramine-non-accumulating barley cultivars, arginine 104 in CYP76M57 is replaced by threonine, which abolished the catalytic activity of CYP76M57 to convert Trp into AMI. These results uncovered the missing committed enzyme of gramine biosynthesis in barley and contribute to the elucidation of the potential functions of CYPs in plants and undiscovered specialized pathways., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Immediate postcraniotomy headache frequently occurs within the first 48 h after surgery. The mechanisms underlying immediate postcraniotomy headache are not yet fully understood, and effective treatments are not yet established. This study aimed to identify the factors associated with immediate postcraniotomy headache in patients who underwent clipping surgery with frontotemporal craniotomy and to examine the effects of these factors on postcraniotomy headache. A total of 51 patients were included in this study. Immediate postcraniotomy headache was defined as pain with numerical rating scale score ≥4 on postoperative day 7. Sixteen patients (31.4%) had immediate postcraniotomy headache. The headache-positive group had a higher incidence of preoperative analgesic use (50.0% vs. 5.7%, respectively, p < 0.001), increased temporal muscle swelling ratio (137.0%±30.2% vs. 112.5%±30.5%, respectively, p = 0.01), and higher postoperative analgesic use (12.9±5.8 vs. 6.7±5.2, respectively, p < 0.001) than the headache-negative group. The risk factors independently associated with immediate postcraniotomy headache were preoperative analgesic use and temporal muscle swelling by >115.15% compared with the contralateral side in the receiver operating characteristic analysis. Postcraniotomy headache was significantly more common in patients with preoperative analgesic use and temporal muscle swelling than in those without (p < 0.001 and p = 0.002, respectively). Altogether, patients with immediate postcraniotomy headache had greater preoperative analgesic use, greater temporal muscle swelling ratio, and higher postoperative analgesic use than those without. Thus, temporal muscle swelling is a key response to immediate postcraniotomy headache.

Objective: To investigate differences in uptake regions between methyl- 11 C-L-methionine positron emission tomography ( 11 C-MET PET) and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI), and their impact on dose distribution, including changing of the threshold for tumor boundaries., Methods: Twenty consecutive patients with grade 3 or 4 glioma who had recurrence after postoperative radiotherapy (RT) between April 2016 and October 2017 were examined. The study was performed using simulation with the assumption that all patients received RT. The clinical target volume (CTV) was contoured using the Gd-enhanced region (CTV(Gd)), the tumor/normal tissue (T/N) ratios of 11 C-MET PET of 1.3 and 2.0 (CTV (T/N 1.3), CTV (T/N 2.0)), and the PET-edge method (CTV(P-E)) for stereotactic RT planning. Differences among CTVs were evaluated. The brain dose at each CTV and the dose at each CTV defined by 11 C-MET PET using MRI as the reference were evaluated., Results: The Jaccard index (JI) for concordance of CTV (Gd) with CTVs using 11 C-MET PET was highest for CTV (T/N 2.0), with a value of 0.7. In a comparison of pixel values of MRI and PET, the correlation coefficient for cases with higher JI was significantly greater than that for lower JI cases (0.37 vs. 0.20, P = 0.007). D50% of the brain in RT planning using each CTV differed significantly (P = 0.03) and that using CTV (T/N 1.3) were higher than with use of CTV (Gd). V90% and V95% for each CTV differed in a simulation study for actual treatment using CTV (Gd) (P = 1.0 × 10 -7 and 3.0 × 10 -9 , respectively) and those using CTV (T/N 1.3) and CTV (P-E) were lower than with CTV (Gd)., Conclusions: The region of 11 C-MET accumulation is not necessarily consistent with and larger than the Gd-enhanced region. A change of the tumor boundary using 11 C-MET PET can cause significant changes in doses to the brain and the CTV., (© 2024. The Author(s).)

Background: Spontaneous intracranial hypotension (SIH) is a rare condition characterized by positional headache, for which contrast-enhanced magnetic resonance imaging (MRI) is the preferred diagnostic method. Although MRI reveals characteristic findings, head computed tomography (CT) is usually the first diagnostic step, but identifying features of SIH on CT is often difficult. This study was specifically designed to evaluate the utility of head CT in detecting upper cervical epidural venous engorgement as a sign of SIH., Observations: Of 24 patients with SIH diagnosed between March 2011 and May 2023, 10 did not undergo upper cervical CT. In the remaining 14 patients, engorgement of the upper cervical epidural venous plexus was observed. CT detection rates were consistent with MRI for spinal fluid accumulation or dural thickening. After treatment, in 92.9% of patients, the thickness of the epidural venous plexus decreased statistically significantly from 4.8 ± 1.3 mm to 3.6 ± 1.2 mm., Lessons: This study suggests that upper cervical spine CT focused on epidural venous engorgement may be helpful in the initial diagnosis of SIH and may complement conventional MRI evaluation. Extending CT imaging to the upper cervical spine will improve the diagnostic accuracy of patients with positional headaches suspected to be SIH.

Hemichorea-hemiballism (HCHB) due to transient ischemic attacks (TIAs) is rare. An 83-year-old woman had repeated episodes of right-sided HCHB for 3 months. Magnetic resonance (MR) angiography demonstrated occlusion of the left carotid and middle cerebral arteries and severe stenosis of the innominate artery, and 24-hour ambulatory blood pressure monitoring showed a blood pressure decrease of >20 mmHg after each meal. We speculated that HCHB developed as TIAs due to hemodynamic failure in the left cerebral hemisphere, caused by a combination of severe stenosis of the innominate artery concomitant with occlusion of the left carotid and middle cerebral arteries as well as postprandial hypotension.

Background: Traditional brain activity monitoring via scalp electroencephalography (EEG) offers limited resolution and is susceptible to artifacts. Endovascular electroencephalography (eEEG) emerged in the 1990s. Despite early successes and potential for detecting epileptiform activity, eEEG has remained clinically unutilized. This study aimed to further test the capabilities of eEEG in detecting lateralized epileptic discharges in animal models. We hypothesized that eEEG would be able to detect lateralization. The purpose of this study was to measure epileptiform discharges with eEEG in animal models with lateralization in epileptogenicity., Materials and Methods: We inserted eEEG electrodes into the transverse sinuses of three pigs, and subdural electrodes (SDs) on the surfaces of the left and right hemispheres. We induced epileptogenicity with penicillin in the left brain of pigs F00001 and F00003, and in the right brain of pig F00002. The resulting epileptiform discharges were measured by eEEG electrodes placed in the left and right transverse sinuses, and conducted comparisons with epileptiform discharges from SDs. We also had 12 neurological physicians interpret measurement results from eEEG alone and determine the side (left or right) of epileptogenicity., Results: Three pigs were evaluated for epileptiform discharge detection using eEEG: F00001 (7 months old, 14.0 kg), F00002 (8 months old, 15.6 kg), and F00003 (8 months old, 14.4 kg). The eEEG readings were compared with results from SDs, showing significant alignment across all subjects (p < 0.001). The sensitivity and positive predictive values (PPV) were as follows: F00001 had 0.93 and 0.96, F00002 had 0.99 and 1.00, and F00003 had 0.98 and 0.99. Even though one of the neurological physicians got all sides incorrect, all other assessments were correct. Upon post-experimental dissection, no abnormalities were observed in the brain tissue or in the vascular damage at the site where the eEEG was placed, based on pathological evaluation., Conclusion: With eEEG, lateralization can be determined with high sensitivity (>0.93) and PPV (>0.95) that appear equivalent to those of subdural EEG in the three pigs. This lateralization was also discernible by neurological physicians on visual inspection., Competing Interests: We wish to draw the attention of the Editor to the following facts which may be considered as potential conflicts of interest and to significant financial contributions to this work. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome except for Yuju Matsumaru (YuM). This research was supported by the 10.13039/100009619Japan Agency for Medical Research and Development (10.13039/100009619AMED) under grant number JP23he0122011. One author (YuM) is the CEO of E.P. Medical Inc. (Tokyo, Japan). We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that any aspect of the work covered in this manuscript that has involved either experimental animals or human patients has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript. We understand that the first author and corresponding author are the contact for the editorial process (including Editorial Manager and direct communications with the office). I, Ayataka Fujimoto, am responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author and which has been configured to accept email from Ayataka Fujimoto (afujimotoscienceacademy@gmail.com)., (© 2024 Published by Elsevier Ltd.)

Background: Rebleeding after hemostasis of the gastroduodenal ulcer (GDU) is one of the indicators associated with death among GDU patients. However, there are few studies on risk score that contribute to rebleeding after endoscopic hemostasis of bleeding peptic ulcers., Aims: The aim of this study was to identify factors associated with rebleeding, including patient factors, after endoscopic hemostasis of bleeding gastroduodenal ulcers and to stratify the risk of rebleeding., Methods: We retrospectively enrolled 587 consecutive patients who were treated for Forrest Ia to IIa bleeding gastroduodenal ulcers with endoscopic hemostasis at three institutions. Risk factors associated with rebleeding were assessed using univariate and multivariate logistic regression analyses. The Rebleeding Nagoya University (Rebleeding-N) scoring system was developed based on the extracted factors. The Rebleeding-N score was internally validated using bootstrap resampling methods., Results: Sixty-four patients (11%) had rebleeding after hemostasis of gastroduodenal ulcers. Multivariate logistic regression analysis revealed four independent rebleeding risk factors: blood transfusion, albumin <2.5, duodenal ulcer, and diameter of the exposed vessel ≧2 mm. Patients with 4 risk factors in the Rebleeding-N score had a 54% rebleeding rate, and patients with 3 risk factors had 44% and 25% rebleeding rates. In the internal validation, the mean area under the curve of the Rebleeding-N score was 0.830 (95% CI = 0.786-0.870)., Conclusions: Rebleeding after clip hemostasis of bleeding gastroduodenal ulcers was associated with blood transfusion, albumin <2.5, diameter of the exposed vessel ≧2 mm, and duodenal ulcer. The Rebleeding-N score was able to stratify the risk of rebleeding., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize bacterial riboflavin-based metabolites as activating antigens. Although MAIT cells are found in tissues, it is unknown whether any host tissue-derived antigens exist. Here, we report that a sulfated bile acid, cholic acid 7-sulfate (CA7S), binds the nonclassical MHC class I protein MR1 and is recognized by MAIT cells. CA7S is a host-derived metabolite whose levels were reduced by more than 98% in germ-free mice. Deletion of the sulfotransferase 2a family of enzymes ( Sult2a1-8 ) responsible for CA7S synthesis reduced the number of thymic MAIT cells in mice. Moreover, recognition of CA7S induced MAIT cell survival and the expression of a homeostatic gene signature. By contrast, recognition of a previously described foreign antigen, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU), drove MAIT cell proliferation and the expression of inflammatory genes. Thus, CA7S is an endogenous antigen for MAIT cells, which promotes their development and function.

The acetal ( O -glycoside) bonds of glycans and glycoconjugates are chemically and biologically vulnerable, and therefore C -glycosides are of interest as more stable analogs. We hypothesized that, if the O -glycoside linkage plays a vital role in glycan function, the biological activities of C -glycoside analogs would vary depending on their substituents. Based on this idea, we adopted a "linkage-editing strategy" for the creation of glycan analogs (pseudo-glycans). We designed three types of pseudo-glycans with CH 2 and CHF linkages, which resemble the O -glycoside linkage in terms of bond lengths, angles, and bulkiness, and synthesized them efficiently by means of fluorovinyl C -glycosylation and selective hydrogenation reactions. Application of this strategy to isomaltose (IM), an inducer of amylase expression, and α-GalCer, which activates iNKT cells, resulted in the discovery of CH 2 -IM, which shows increased amylase production ability, and CHF-α-GalCer, which shows activity opposite that of native α-GalCer, serving as an antagonist of iNKT cells.

Hidden bow hunter's syndrome (HBHS) is a rare disease in which the vertebral artery (VA) occludes in a neutral position but recanalizes in a particular neck position. We herein report an HBHS case and assess its characteristics through a literature review. A 69-year-old man had repeated posterior-circulation infarcts with right VA occlusion. Cerebral angiography showed that the right VA was recanalized only with neck tilt. Decompression of the VA successfully prevented stroke recurrence. HBHS should be considered in patients with posterior circulation infarction with an occluded VA at its lower vertebral level. Diagnosing this syndrome correctly is important for preventing stroke recurrence.

Objective: Intraoperative rebleeding during endovascular treatment for ruptured intracranial aneurysms is associated with poor prognosis. Lumbar drainage is performed preoperatively to control intracranial pressure; however, it is associated with a risk of brain herniation or rebleeding because intracranial pressure may change rapidly. Therefore, this study aimed to examine the efficacy and safety of preoperative lumbar drainage., Methods: This retrospective study enrolled 375 patients who underwent endovascular treatment of ruptured intracranial aneurysms at our institution between April 2013 and March 2018. The incidence of rebleeding and clinical outcomes were compared between patients who did and did not undergo preoperative lumbar drainage., Results: Among the 375 patients with ruptured intracranial aneurysms, 324 (86.0%) and 51 (14.0%) patients did and did not undergo lumbar drainage, respectively. The incidence of rebleeding was 11/324 (3.4%) and 2/51 (3.9%) in lumbar drainage and nonlumbar drainage groups, respectively, with no statistical differences (p = 0.98). Of the rebleeding cases, 9/11 (81%) and 2/2 (100%) in lumbar drainage and nonlumbar drainage groups, respectively, were due to intraoperative bleeding, and 2/11 (19%) in the lumbar drainage group, the causes of the rebleeding were undetermined. The incidence of symptomatic vasospasm did not differ significantly between the groups (13.2% vs. 11.8%, P = 0.776), while the incidence of hydrocephalus (24.6% vs. 11.8%, P = 0.043) and meningitis (15.2% vs. 5.9%, P = 0.075) were slightly higher in the lumbar drainage group. Favorable clinical outcomes (modified Rankin Scale score <2) at discharge were less frequent in the lumbar drainage group (55.3% vs. 70.0%, P = 0.051). No significant differences were observed in the propensity score-matched analysis., Conclusion: Lumbar drainage before endovascular treatment for ruptured intracranial aneurysms is a safe procedure that does not increase the incidence of rebleeding., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, or publication of this article., (©2024 The Japanese Society for Neuroendovascular Therapy.)

In the transsylvian (TS) approach, as characterized by clipping surgery, the presurgical visualization of the superficial middle cerebral vein (SMCV) can help change the surgical approach to ensure safe microsurgery. Nevertheless, identifying preoperatively the venous structures that are involved in this approach is difficult. In this study, we investigated the venous structures that are involved in the TS approach using three-dimensional (3D) rotational venography (3D-RV) and evaluated the effectiveness of this method for presurgical simulation. Patients who underwent 3D-RV between August 2018 and June 2020 were involved in this retrospective study. The 3D-RV and partial maximum intensity projection images with a thickness of 5 mm were computationally reconstructed. The venous structures were subdivided into the following three portions according to the anatomic location: superficial, intermediate, and basal portions. In the superficial portion, predominant frontosylvian veins were observed on 31 (41%) sides, predominant temporosylvian veins on seven (9%) sides, and equivalent fronto- and temporosylvian veins on 28 (37%) sides. The veins in the intermediate (deep middle cerebral and uncal veins) and basal portions (frontobasal bridging veins) emptied into the SMCV on 57 (75%) and 34 (45%) sides, respectively. The 3D-RV images were highly representative of the venous structures observed during microsurgery. In this study, 3D-RV was utilized to capture the details of the venous structures from the superficial to the deep portions. Presurgical simulation of the venous structures that are involved in the TS approach using 3D-RV may increase the safety of microsurgical approaches.

[Proposal] Here, we retrospectively evaluate risk factors for radiation necrosis and local recurrence after PBT for skull base chordoma or chondrosarcoma. [Patients and Methods] We analyzed 101 patients who received PBT for skull base chordomas and chondrosarcomas from January 1989 to February 2021. Multivariable logistic regression models were applied for local recurrence, temporal lobe radiation necrosis rates, and temporal lobe radiation necrosis. [Results] In multivariate analysis, chordoma and large tumor size were independent significant factors for local recurrence. The 1-, 2-, 3-, 4- and 5-year local recurrence rates were 3.9%, 16.9%, 20.3%, 28.5% and 44.0% for chordoma and 0%, 0%, 0%, 0% and 7.1% for chondrosarcoma, respectively. The local recurrence rates of small tumors (<30 mm) were 4.3%, 14.7%, 17.7%, 17.7% and 25.9%, and those for large tumors were 3.6%, 15.1%, 19.2%, 32.7% and 59.6%, respectively. In multivariate analysis, BED Gy 10 and total dose were risk factors for radiation necrosis. [Conclusions] For skull base chordoma and chondrosarcoma, the risk factors of local recurrence were chordoma and large tumor size, and those of radiation necrosis were BED Gy 10 and total dose, respectively. DVH analysis is needed to investigate the risk factors for brain necrosis in more detail.