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Ice is the most fundamental hydrogen-bonded system in which the hydrogen nuclear quantum effect significantly impacts the structure and relevant thermochemical and spectroscopic properties. While ice was experimentally investigated using proton nuclear magnetic resonance spectroscopy more than 40 years ago, the corresponding theoretical investigations have been rarely reported due to the difficulty in evaluating how the proton nuclear quantum effect influences the spectral characteristics of such a condensed material. In this study, we applied a combination of the ONIOM and multicomponent molecular orbital (MC_MO) methods for calculating the anisotropic and isotropic components of the nuclear magnetic shielding tensor of the hexagonal ice crystal to quantify the effects of nuclear quantum fluctuations on the spectroscopic properties of ice. The nuclear magnetic shielding values computed by incorporating the hydrogen nuclear quantum effect reasonably agree with the experimental values. The nuclear quantum effects were found to increase the anisotropic component of the magnetic shielding tensor while decreasing the isotropic component. Such a difference can be explained by their distinct dependence on the electrostatic field and hydrogen-bonding structural parameters.

Background and Objectives: Intravenous indocyanine green (IV-ICG) videoangiography is commonly performed to detect blood flow in the microscopic view. However, intra-arterial ICG (IA-ICG) videoangiography provides high-contrast imaging, repeatability within a short period of time, and clear-cut separation of the arterial and venous phases compared with IV-ICG. These features are useful for detecting retrograde venous drainage (RVD) and shunt occlusion in arteriovenous fistulae (AVF) surgery. This study aimed to investigate whether IA-ICG videoangiography can be repeatable within a short period of time and be useful for detecting RVD and shunt occlusion in cranial- and craniocervical junction (CCJ)-AVF surgery., Methods: Between January 2012 and December 2022, 50 patients were treated with endovascular or surgical intervention for cranial- and CCJ-AVF at Tokushima University Hospital. Of these, 5 patients (6 lesions) underwent open surgery with IA-ICG videoangiography in a hybrid operating room. We analyzed the data of these 5 patients (6 lesions)., Results: There were 4/patient (median, range 2-12) and 3.5/lesion (median, range 2-10) intraoperative IA-ICG runs. IA-ICG videoangiography detected RVD in all patients. Clearance of IA-ICG-induced fluorescence was achieved within 30 seconds in all patients at each region of interest. After the disconnection of the fistulae, IA-ICG videoangiography and intraoperative digital subtraction angiography (DSA) confirmed the disappearance of RVD in all patients. There were no complications associated with IA-ICG videoangiography., Conclusion: This study showed that IA-ICG videoangiography is repeatable within a short period of time before and after obliteration and can be useful for detecting RVD and shunt occlusion in cranial- and CCJ-AVF surgery. IA-ICG videoangiography also allows intraoperative DSA studies in a hybrid operating room. Considering the recent advancements in hybrid operating rooms, combining IA-ICG videoangiography with intraoperative DSA is a useful strategy for cranial- and CCJ-AVF surgery., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Cerebral microbleeds (CMBs) due to traumatic brain injuries (TBI) have been shown to lead to cognitive decline and impairment. CMBs caused by TBI may be associated with pathophysiological mechanisms involving inflammation and the accumulation of amyloid-β (Aβ), tau, and phosphorylated tau (p-tau), contributing to cognitive abnormalities. However, their relationships remain unclear., Objectives: To test our hypothesis that Aβ, tau, and p-tau are accumulated and regulated separately in mice with injuries imitating CMBs from TBI, we studied., Methods: Seven-week-old C57BL/6 male mice were injected with 15 μL of heparinized autologous blood or saline by micro-syringe into the front lobe. Expression profiles and regulation of Aβ, tau, and p-tau were assessed immunohistochemically over time., Results: On day 7 after blood injection, Iba-1 + and S100B + cells in damaged cortex adjacent to the injection site were higher than saline injection group and non-injected sham. On days 3-14, Aβ deposition were gradually increased but normalized by day 28. In contrast, tau/p-tau deposition gradually increased during days 14-28 and dispersed along the corticomedullary junction adjacent to hem deposits, indicating different expression profiles from Aβ. Deposits of Aβ, but not tau/p-tau, were phagocytosed by CD163 + macrophages increased by Gc-protein macrophage-activating factor during days 7-28, suggesting different mechanisms of deposition and regulation between Aβ and tau/p-tau., Conclusion: Deposition and regulation differ between Aβ and tau/p-tau in mice with injuries mimicking CMBs from TBI. Further clarification of relationships between the pathologies of cognitive impairment and their neurodegenerative consequences is needed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Revascularization for common carotid artery (CCA) occlusion might be difficult. We reported our strategy for revascularizing CCA occlusion by giant clots. A 94-year-old woman was transferred to our hospital because of right hemiparesis and aphasia. CCA occlusion and giant clots were detected on ultrasonography. We performed mechanical thrombectomy using a 9-Fr balloon-guiding catheter, stent retriever, and aspiration catheter through a 9-Fr long-sheath introducer [long-sheath introducer-assisted revascularization (L-SHARE) technique]. We successfully recanalized CCA occlusion using this method. The L-SHARE technique might be useful for recanalization of CCA occlusion.

Structure-function relationships in proteins have been one of the crucial scientific topics in recent research. Heme proteins have diverse and pivotal biological functions. Therefore, clarifying their structure-function correlation is significant to understand their functional mechanism and is informative for various fields of science. In this study, we constructed convolutional neural network models for predicting protein functions from the tertiary structures of heme-binding sites (active sites) of heme proteins to examine the structure-function correlation. As a result, we succeeded in the classification of oxygen-binding protein (OB), oxidoreductase (OR), proteins with both functions (OB-OR), and electron transport protein (ET) with high accuracy. Although the misclassification rate for OR and ET was high, the rates between OB and ET and between OB and OR were almost zero, indicating that the prediction model works well between protein groups with quite different functions. However, predicting the function of proteins modified with amino acid mutation(s) remains a challenge. Our findings indicate a structure-function correlation in the active site of heme proteins. This study is expected to be applied to the prediction of more detailed protein functions such as catalytic reactions.

Background: Intravenous recombinant tissue plasminogen activator (IV rt-PA) and endovascular treatment have been performed for severe large vessel occlusion (LVO) and the results have been reported at high levels of evidence. However, acute treatment for LVO with mild symptom remains controversial. We retrospectively examined prognostic factors for LVO with mild symptoms., Method: We studied retrospectively the patients within 24 h of onset with large vessel occlusion with NIHSS score ??5. Outcomes were evaluated by modified Rankin Scale (mRS) at 90 days, with 0?2 defined as a good outcome and 3?6 as a poor outcome. Clinical characteristics of each case were examined., Result: Participants comprised 76 patients. Of the 76 patients. ICA occlusion showed good outcome in 17?/?19 cases (90%), whereas MCA occlusion showed good outcome in 36?/?54 cases (67%). Among the 14 cases showing positive results for distal intraarterial signal (d-IAS), outcomes were good in 6 cases (43%). On the other hand, the 32 d-IAS-negative cases showed good outcome in 28 cases (88%). Outcomes were thus significantly poorer for d-IAS-positive cases., Conclusion: MCA occlusion is associated with poor prognosis, even with NIHSS score ??5, and d-IAS may provide a predictor. J. Med. Invest. 70 : 22-27, February, 2023.

Objective: An understanding of the complex morphology of an arteriovenous malformation (AVM) is important for successful resection. We have previously reported the utility of intra-arterial indocyanine green (ICG) videoangiography for this purpose, but that method cannot detect the angioarchitecture covered by brain tissue. 3-dimensional (3D) multimodal fusion imaging is reportedly useful for this same purpose, but cannot always visualize the exact angioarchitecture due to poor source images and processing techniques. This study examined the results of utilizing both techniques in patients with AVMs., Methods: Both techniques were applied in 12 patients with AVMs. Both images were compared with surgical views and evaluated by surgeons., Results: Although evaluations for identifying superficial feeders by ICG videoangiography were high in all cases, the more complicated the AVM, the lower the evaluation by 3D multimodal fusion imaging. Conversely, evaluation of the estimated range of the nidus was high in all cases by 3D multimodal fusion imaging, but low in all but one case by ICG videoangiography. Nidus flow reduction was recognized by Flow 800 analysis obtained after ICG videoangiography., Conclusions: These results showed that utilizing both techniques together was more useful than each modality alone in AVM surgery. This was particularly effective in identifying superficial feeders and estimating the range of the nidus. This technique is expected to offer an optimal tool for AVM surgery., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The gain of the microchannel plate temporally drops after an ion initiates an electron avalanche. Electron multiplication was expected to deplete the charge from the microchannel wall and produce the depleted charge (wall charge). Moreover, it was reported that the gain drop occurred not only in the activated channels, where the electrons are multiplied, but also in the surrounding channels. One mechanism of the gain-drop spatial extension has been considered as that the wall charges in the activated channels change the electric field in the surrounding channels. Anacker et al . assumed that the wall charge is a uniform line charge; the gain-drop spatial extent should be proportional to the amount of the wall charges. We considered that the wall charges exponentially increased in the channel toward the exit. In this study, the electric field produced by the wall charges was calculated, considering the distribution of the wall charges. The transverse electric field generated by the wall charges was expected to disturb the electron trajectory near the channel exit and decrease the number of secondary electrons emitted per collision (gain per collision), resulting in a gain drop. The gain per collision was calculated to decrease by 22% for the position where the gain decreased significantly in the presence of the transverse electric field of 3×10 5 V/m. In our model, the gain-drop spatial extent extended proportionally to the square root of the wall charges when the distance from the activated channel exceeded 50 μm., (Copyright © 2023 Hiroshi Kobayashi, Toshinobu Hondo, Yasuo Kanematsu, Motohiro Suyama, and Michisato Toyoda.)

The major cytoskeleton protein actin undergoes cyclic transitions between the monomeric G-form and the filamentous F-form, which drive organelle transport and cell motility. This mechanical work is driven by the ATPase activity at the catalytic site in the F-form. For deeper understanding of the actin cellular functions, the reaction mechanism must be elucidated. Here, we show that a single actin molecule is trapped in the F-form by fragmin domain-1 binding and present their crystal structures in the ATP analog-, ADP-Pi-, and ADP-bound forms, at 1.15-Å resolutions. The G-to-F conformational transition shifts the side chains of Gln137 and His161, which relocate four water molecules including W1 (attacking water) and W2 (helping water) to facilitate the hydrolysis. By applying quantum mechanics/molecular mechanics calculations to the structures, we have revealed a consistent and comprehensive reaction path of ATP hydrolysis by the F-form actin. The reaction path consists of four steps: 1) W1 and W2 rotations; 2) P G -O 3B bond cleavage; 3) four concomitant events: W1-PO 3 - formation, OH - and proton cleavage, nucleophilic attack by the OH - against P G , and the abstracted proton transfer; and 4) proton relocation that stabilizes the ADP-Pi-bound F-form actin. The mechanism explains the slow rate of ATP hydrolysis by actin and the irreversibility of the hydrolysis reaction. While the catalytic strategy of actin ATP hydrolysis is essentially the same as those of motor proteins like myosin, the process after the hydrolysis is distinct and discussed in terms of Pi release, F-form destabilization, and global conformational changes.

Heme proteins serve diverse and pivotal biological functions. Therefore, clarifying the mechanisms of these diverse functions of heme is a crucial scientific topic. Distortion of heme porphyrin is one of the key factors regulating the chemical properties of heme. Here, we constructed convolutional neural network models for predicting heme distortion from the tertiary structure of the heme-binding pocket to examine their correlation. For saddling, ruffling, doming, and waving distortions, the experimental structure and predicted values were closely correlated. Furthermore, we assessed the correlation between the cavity shape and molecular structure of heme and demonstrated that hemes in protein pockets with similar structures exhibit near-identical structures, indicating the regulation of heme distortion through the protein environment. These findings indicate that the tertiary structure of the heme-binding pocket is one of the factors regulating the distortion of heme porphyrin, thereby controlling the chemical properties of heme relevant to the protein function; this implies a structure-function correlation in heme proteins.

Background and Purpose: An aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na + /K + -ATPase (ATP1α3)., Methods: Ten-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet., Results: Six weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05)., Conclusions: Regulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs., (© 2022. The Author(s).)

Objective: Subarachnoid hemorrhage (SAH) due to intracranial aneurysm (IA) rupture is often a devastating event. Since the incidence of SAH increases especially in menopause, it is crucial to clarify the detailed pathogenesis of these events. The activation of vascular nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes has been studied in ischemic stroke and cardiovascular disease. However, the role of NLRP3 in IA rupture still needs to be explained. The authors sought to test their hypothesis that, under estrogen-deficient conditions, activation of NLRP3 inflammasomes via downregulation of the estrogen receptor (ER) facilitates IA rupture., Methods: Ten-week-old female Sprague Dawley rats with and without oophorectomy were subjected to hemodynamic changes and hypertension (OVX+/HT and OVX-/HT, respectively) and fed a high-salt diet. Separately, using human brain endothelial cells (HBECs) and human brain smooth muscle cells (HBSMCs), the authors tested the effect of NLRP3 under estrogen-free conditions and in the presence of estradiol or of ER agonists., Results: In OVX+/HT rats, the frequency of IA rupture was significantly higher than in OVX-/HT rats (p = 0.03). In the left posterior cerebral artery prone to rupture in OVX+/HT rats, the levels of the mRNAs encoding ERα and Sirt1, but not of that encoding ERβ, were decreased, and the levels of the mRNAs encoding NLRP3, interleukin-1β (IL-1β), and matrix metalloproteinase 9 (MMP-9) were elevated. Immunohistochemical analysis demonstrated that the expression profiles of these proteins correlated with their mRNA levels. Treatment with an ER modulator, bazedoxifene, normalized the expression profiles of these proteins and improved SAH-free survival. In HBECs and HBSMCs under estrogen-free conditions, the depletion of ERα and Sirt1 and the accumulation of NLRP3 were counteracted by exposure to estradiol or to an ERα agonist but not to an ERβ agonist., Conclusions: To the authors' knowledge, this work represents the first demonstration that, in an aneurysm model under estrogen-deficient conditions, the depletion of ERα and Sirt1 may contribute to activation of the NLRP3/IL-1β/MMP-9 pathway, facilitating the rupture of IAs in the estrogen-deficient rat IA rupture model.

Purpose: Arterial spin labeling (ASL) and diffusion-weighted imaging (DWI) are useful for assessing hyperperfusion and cytotoxic edema, respectively, caused by acute seizures. This study investigated the clinical characteristics associated with normal ASL findings and DWI abnormalities in patients with acute seizures., Methods: Overall, 41 patients with ASL and DWI images that were obtained within 48 h of focal onset seizure diagnosis, due to epilepsy or acute symptomatic seizures, were divided into groups based on initial ASL findings (ASL-negative vs. ASL-positive), and DWI abnormalities (DWI-negative vs. DWI-positive). The diagnosis was made based on seizure semiology, electroencephalography, and conventional imaging modalities. ASL and DWI abnormalities were based on visual assessment., Results: Of the 41 patients, eight (19.5%) displayed normal ASL findings. The proportion of patients with focal aware seizures (FAS) was significantly higher among ASL-negative patients (62.5%) than that in ASL-positive patients (15.2%); the proportion of patients with focal impaired awareness seizures (FIAS) was significantly lower among ASL-negative patients (12.5%) than that among ASL-positive patients (57.6%). Hyperintensity findings on DWI were observed in 12 patients (29.3%, DWI-positive). The proportion of patients with FIAS was significantly higher among DWI-positive patients (75.0%) than that among DWI-negative patients (37.9%). Multivariate analysis revealed that FAS and FIAS were associated with normal ASL findings (odds ratio [OR]: 21.37, P = 0.010) and DWI abnormalities (OR = 6.11, P = 0.028)., Conclusion: A diagnosis of seizures should not be excluded based on normal ASL findings, especially in patients with FAS. FIAS may be a risk factor for neuronal damage caused by seizure activity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Heme proteins play diverse and important biological roles, from electron transfer and chemical catalysis to oxygen transport and/or storage. Although the distortion of heme porphyrin correlates with the physical properties of heme, such as the redox potential and oxygen affinity, the relationship between heme distortion and the heme protein environment is unclear. Here, we tested the hypothesis that the protein environment of the heme-binding pocket determines heme distortion (conformation). We analyzed the correlations between the amino acid composition of the heme-binding pocket and the magnitude of heme distortion along 12 vibrational modes using machine learning. A correlation was detected in the three lowest vibrational modes. Analysis of heme distortions in nearly the same environments of the heme-binding pocket supported this notion. Our analyses indicate that the heme-binding pocket environment is a major factor impacting the distortion of heme porphyrin along the three lowest vibrational modes. In addition, statistical analysis of the distortion of heme porphyrin revealed that the peaks of distributions of the ruffling and breathing distortions are shifted from 0 (the equilibrium structure). Both the ruffling and breathing distortions are correlated with the redox potential of heme, so that heme molecules with these distortions have a lower redox potential than planar molecules. These findings explain the structure-function relationship of heme.

Background: Mechanical thrombectomy (MT) is an effective treatment for acute cerebral large vessel occlusion (LVO). Complete recanalization of vessels in a single procedure is defined as the first-pass effect (FPE) and is associated with good prognosis. In this study, angiographic clot protruding sign termed the "claw sign," was examined as candidate preoperative imaging factor for predicting the FPE., Methods: We retrospectively analyzed data from 91 consecutive patients treated for acute LVO in the anterior circulation by MT between January 2014 and December 2019. The claw sign was defined as a thrombus that protruded proximally by more than half of the diameter of the parent artery. Radiological findings such as claw sign, clinical and etiological features, and outcomes were compared between groups with and without successful FPE. Multivariate analysis was conducted to evaluate perioperative factors associated with FPE., Results: FPE was achieved in 26 of 91 (28.6%) patients and the claw sign was observed in 34 of 91 (37.4%) patients. The claw sign was significantly more frequent in the successful FPE group than in the failed FPE group (53.8% vs. 30.8%; P = 0.040). After the multivariate analysis, the claw sign was the only pretreatment parameter that could predict FPE (odds ratio, 2.67; 95% confidence interval, 1.01-7.06; P = 0.047)., Conclusion: The claw sign is an angiographic imaging factor that might predict FPE after MT for anterior circulation acute ischemic stroke., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

Recently, deuterium-labeled drugs, such as deutetrabenazine, have attracted considerable attention. Consequently, understanding the reaction mechanisms of deuterium-labeled drugs is crucial, both fundamentally and for real applications. To understand the mechanisms of H- and D-transfer reactions, in this study, we used deuterated anisole as a deutetrabenazine model and computationally considered the nuclear quantum effects of protons, deuterons, and electrons. We demonstrated that geometrical differences exist in the partially and fully deuterated methoxy groups and hydrogen-bonded structures of intermediates and transition states due to the H/D isotope effect. The observed geometrical features and electronic structures are ascribable to the different nuclear quantum effects of protons and deuterons. Primary and secondary kinetic isotope effects (KIEs) were calculated for H- and D-transfer reactions from deuterated and undeuterated anisole, with the calculated primary KIEs in good agreement with the corresponding experimental data. These results reveal that the nuclear quantum effects of protons and deuterons need to be considered when analyzing the reaction mechanisms of H- and D-transfer reactions and that a theoretical approach that directly includes nuclear quantum effects is a powerful tool for the analysis of H/D isotope effects in H- and D-transfer reactions.

The prevalence of chronic subdural hematoma (CSDH) associated with dural metastasis is uncertain, and appropriate treatment strategies have not been established. This study aimed to investigate the characteristics of and appropriate treatment strategies for CSDH associated with dural metastasis. We retrospectively reviewed the charts of 214 patients who underwent surgery for CSDH. The patients were divided into the dural metastasis group (DMG; n = 5, 2.3%) and no dural metastasis group (No-DMG; n = 209, 97.3%). Patient characteristics, treatment, and outcomes were compared between the two groups. Active cancer was detected in 31 out of 214 patients, 5 of whom (16.1%) had dural metastasis. In-hospital death (80.0% vs. 0%; p < 0.001) and recurrence within 14 days (80.0% vs. 2.9%; p < 0.001) and 60 days (80.0% vs. 13.9%; p = 0.002) were significantly prevalent in the DMG. All patients in the DMG developed subdural hematoma re-accumulation requiring emergent surgery because of brain herniation, and patients in the DMG had significantly worse recurrence-free survival (p < 0.001). This relationship remained significant (p < 0.001) even when the analysis was limited to the active cancer cohort (n = 31). CSDH associated with dural metastasis leads to early recurrence and death because of the difficulty in controlling subdural hematoma re-accumulation by common drainage procedures. Depending on the primary cancer status, withdrawal of active treatment and change to palliative care should be discussed after diagnosing CSDH associated with dural metastasis., 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 © 2021 Elsevier Ltd. All rights reserved.)

Aims: Lifestyle-related diseases promote atherosclerosis, a chronic inflammatory disease; however, the molecular mechanism remains largely unknown. Endogenous DNA fragments released under over-nutrient condition provoke sterile inflammation through the recognition by DNA sensors. Here, we investigated the role of stimulator of interferon genes (STING), a cytosolic DNA sensor, in atherogenesis., Methods and Results: Apolipoprotein E-deficient (Apoe-/-) mice fed a western-type diet (WTD), a hypercholesterolaemic mouse model, showed higher STING expression and markers for DNA damage such as γH2AX, p53, and single-stranded DNA (ssDNA) accumulation in macrophages in the aorta compared with wild-type (WT) mice. The level of cGAMP, a STING agonist, in the aorta was higher in Apoe-/- mice. Genetic deletion of Sting in Apoe-/- mice reduced atherosclerotic lesions in the aortic arch, lipid, and macrophage accumulation in plaques, and inflammatory molecule expression in the aorta compared with the control. Pharmacological blockade of STING using a specific inhibitor, C-176, ameliorated atherogenesis in Apoe-/- mice. In contrast, bone marrow-specific STING expression in Apoe-/- mice stimulated atherogenesis. Expression or deletion of STING did not affect metabolic parameters and blood pressure. In vitro studies revealed that STING activation by cGAMP or mitochondrial DNA accelerated inflammatory molecule expression (e.g. TNF-α or IFN-β) in mouse and human macrophages. Activation of nuclear factor-κB and TANK binding kinase 1 was involved in STING-associated vascular inflammation and macrophage activation. Furthermore, human atherosclerotic lesions in the carotid arteries expressed STING and cGAMP., Conclusion: Stimulator of interferon genes stimulates pro-inflammatory activation of macrophages, leading to the development of atherosclerosis. Stimulator of interferon genes signalling may serve as a potential therapeutic target for atherosclerosis., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: In patients with embolic stroke of undetermined source (ESUS), paroxysmal atrial fibrillation (AF) is often diagnosed, however, the risk of paroxysmal AF in ESUS has not been well described. Several studies have suggested a linkage between left atrial (LA) functional parameters and risk of AF in stroke patients. The aim of this study was to assess the role of LA functional parameters as predictors of latent paroxysmal AF in ESUS on admission., Methods: Between January 2015 and December 2019, consecutive stroke patients with suspected ESUS at admission were prospectively included in this study. They were under hospital electrocardiographic monitoring for detection of new-onset AF. Various echocardiographic parameters including left atrial strain were assessed for association with new-onset AF., Results: We gathered 1082 consecutive patients with ischemic stroke. After exclusions, 121 patients with suspected ESUS at admission formed the study cohort. New-onset AF was detected in 46 (38%) patients during hospital electrocardiographic monitoring (median follow-up: 18 days). LA pump and reservoir strains were significantly and independently associated with new-onset AF. Receiver operating characteristic analysis for the association with new-onset AF showed that the areas under the curve (AUCs) of clinical parameters plus one of each strain (LA pump strain: AUC: 0.86±0.04 and LA reservoir strain: AUC: 0.76±0.05) models were significantly better than plus LA volume index (AUC: 0.68±0.04, compared p-values <0.05)., Conclusions: LA strain was significantly associated with new development of AF. Patients with impaired LA function at admission should be carefully monitored to find AF., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Cerebral arteriovenous malformations (cAVMs) represent tangles of abnormal vasculature without intervening capillaries. High-pressure vascular channels due to abnormal arterial and venous shunts can lead to rupture. Multiple pathways are involved in the pathobiology of cAVMs including inflammation and genetic factors such as KRAS mutations. Neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs), plays a multifunctional role in infection, inflammation, thrombosis, intracranial aneurysms, and tumor progression. However, the relationship between NETs and the pathobiology of cAVMs remains unknown. We tested whether NETs play a role in the pathobiology of cAVMs., Methods: We analyzed samples from patients who had undergone surgery for cAVM and immunohistochemically investigated expression of citrullinated histone H3 (CitH3) as a marker of NETs. CitH3 expression was compared among samples from cAVM patients, epilepsy patients, and normal human brain tissue. Expressions of thrombotic and inflammatory markers were also examined immunohistochemically in samples from cAVM patients., Results: Expression of CitH3 derived from neutrophils was observed intravascularly in all cAVM samples but not other samples. Nidi of AVMs showed migration of many Iba-I-positive cells adjacent to the endothelium and endothelial COX2 expression, accompanied by expression of IL-6 and IL-8 in the endothelium and intravascular neutrophils. Unexpectedly, expression of CitH3 was not necessarily localized to the vascular wall and thrombus., Conclusions: Our results offer the first evidence of intravascular expression of NETs, which might be associated with vascular inflammation in cAVMs., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Mortality rate after subarachnoid hemorrhage due to rupture of vertebral artery dissecting aneurysms (VADAs) is high; endovascular coil trapping is the first-line therapy to prevent rerupture. To select optimal treatments, the positional relationship between the VADA and posterior inferior cerebellar artery (PICA) and the morphology of the contralateral vertebral artery must be considered, and outcome predictors of different treatment methods and their possible complications must be identified., Methods: We retrospectively studied 44 patients with ruptured VADAs who had undergone endovascular or surgical treatment. VADA morphology was assessed on conventional preoperative angiograms, and VADAs were categorized based on their site in relation to the PICA. VADA site, treatment method, and complications were used to identify prognostic factors., Results: The sites of the 44 VADAs were PICA-proximal (n = 3), PICA-distal (n = 22), PICA-absent (n = 7), and PICA-involved (n = 12). Treatments included internal coil trapping (n = 30), proximal coil occlusion (n = 5), and stent placement (n = 3); surgical flow alteration via an occipital artery-PICA bypass and ligation at the proximal vertebral artery and the PICA origin was performed in 6 patients. Periprocedural rebleeding was associated with a poor outcome. Internal coil trapping prevented the rerupture of PICA-proximal and PICA-absent VADAs, and flow alteration prevented rerupture of PICA-involved VADAs; there were no complications directly attributable to these procedures., Conclusions: Periprocedural rebleeding was a poor prognostic factor. Internal trapping of PICA-proximal and PICA-absent VADAs and flow alteration in PICA-involved VADAs prevented rerupture., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Nitric oxide (NO) reductase from the fungus Fusarium oxysporum is a P450-type enzyme (P450nor) that catalyzes the reduction of NO to nitrous oxide (N 2 O) in the global nitrogen cycle. In this enzymatic reaction, the heme-bound NO is activated by the direct hydride transfer from NADH to generate a short-lived intermediate ( I ), a key state to promote N-N bond formation and N-O bond cleavage. This study applied time-resolved (TR) techniques in conjunction with photolabile-caged NO to gain direct experimental results for the characterization of the coordination and electronic structures of I TR freeze-trap crystallography using an X-ray free electron laser (XFEL) reveals highly bent Fe-NO coordination in I , with an elongated Fe-NO bond length (Fe-NO = 1.91 Å, Fe-N-O = 138°) in the absence of NAD + TR-infrared (IR) spectroscopy detects the formation of I with an N-O stretching frequency of 1,290 cm -1 upon hydride transfer from NADH to the Fe 3+ -NO enzyme via the dissociation of NAD + from a transient state, with an N-O stretching of 1,330 cm -1 and a lifetime of ca. 16 ms. Quantum mechanics/molecular mechanics calculations, based on these crystallographic and IR spectroscopic results, demonstrate that the electronic structure of I is characterized by a singly protonated Fe 3+ -NHO •- radical. The current findings provide conclusive evidence for the N 2 O generation mechanism via a radical-radical coupling of the heme nitroxyl complex with the second NO molecule., Competing Interests: The authors declare no competing interest.

Introduction: Urinary titin is a biomarker of muscle atrophy, which is a serious complication after stroke. However, there are currently no clinical data regarding urinary titin in stroke patients., Methods: Consecutive stroke patients admitted to the stroke care unit were included. Spot urine samples were collected immediately after admission, and on days 3, 5, and 7. The primary outcome was the trend of urinary titin in patients after acute stroke. The secondary outcomes included the association between the peak urinary titin level and the modified Rankin Scale (mRS) score, the National Institutes of Health Stroke Scale (NIHSS) score, and the Barthel index (BI) upon hospital discharge. Multivariate analysis was adjusted for age, sex, NIHSS at admission, and the peak urinary titin to predict poor outcome (mRS 3-6)., Results: Forty-one patients were included (29 male; age, 68 ± 15 years), 29 had ischemic stroke, 8 had intracerebral hemorrhage, and 4 had subarachnoid hemorrhage. The levels of urinary titin on days 1, 3, 5, and 7 were 9.9 (4.7-21.1), 16.2 (8.6-22.0), 8.9 (4.8-15.2), and 8.7 (3.6-16.2) pmol/mg Cr, respectively. The peak urinary titin level was associated with the mRS score (r = 0.55, p < 0.01), the NIHSS score (r = 0.72, p < 0.01), and the BI (r = -0.59, p < 0.01) upon hospital discharge. In multivariate analysis, the peak urinary titin was associated with poor outcome (p = 0.03)., Conclusions: Urinary titin rapidly increased after stroke and was associated with impaired functional outcomes at hospital discharge., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A 36-year-old woman who had been diagnosed with systemic lupus erythematosus (SLE) was admitted to our hospital due to increasing disease SLE activity. Despite the intensification of immunosuppressive treatment, headache newly developed and worsened. Magnetic resonance imaging (MRI) revealed spreading of a high-intensity area along the sulci of the bilateral cerebellar hemispheres. She was diagnosed with neuropsychiatric SLE and methylprednisolone (mPSL) pulse therapy was started. However, consciousness disorder due to cerebellar oedema with obstructive hydrocephalus appeared and required decompressive craniectomy. The histological findings of the biopsy specimens from cerebellar vermis were compatible with features of vasculitis. She was successfully treated adding intravenous cyclophosphamide therapy.

Background: The Alberta Stroke Program Early CT score (ASPECTS) of patients with acute ischemic stroke at the time of admission varies. It is crucial to select appropriate methods of treatment, such as recombinant tissue-plasminogen activator, and/or endovascular thrombectomy. According to the recent guidelines, endovascular thrombectomy for patients with large vessel occlusion (LVO) and lesion of ischemic tissue that was not yet infarcted is effective. This result demonstrates the importance of patient selection based on neuroradiological imaging. However, there are many patients who are judged as ineligibility for recanalization therapy because of presence of large ischemic core, indicating unfavorable ASPECTS, at the time of admission. We investigated the factors associated with favorable diffusion-weighted image (DWI)-ASPECTS score at the time of admission., Methods: We studies patients with LVO within 24 h from onset who were admitted into our hospital. We divided them into two groups, with favorable DWI-ASPECTS (≥6), and unfavorable DWI-ASPECTS (<6) at the time of admission. We investigated factors associated with favorable DWI-ASPECTS by evaluation of our patients' severity of clinical symptom, etiology, and radiological findings., Results: This study showed that mild white matter lesion (Fazekas scale ≤1), absence of internal carotid artery (ICA) occlusion and cardioembolic stroke were independent factor of favorable DWI-ASPECTS at the time of admission. (odds ratio 12.92, p <  0.001, odds ratio 0.31, p =  0.001, odds ratio 0.16, p = 0.001, respectively) CONCLUSIONS: Absence of severe white matter lesion, cardioembolic stroke, and ICA occlusion might be associated with favorable DWI-ASPECTS at the time of admission., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Heme participates in a wide range of biological functions such as oxygen transport, electron transport, oxygen reduction, transcriptional regulation and so on. While the mechanism of each function has been investigated for many heme proteins, the origin of the diversity of the heme functions is still unclear and a crucial scientific issue. We have constructed a database of heme proteins, named Python-based database and analyzer for DIStortion of Heme porphyrin (PyDISH), which also contains some analysis tools. The aim of PyDISH is to integrate the information on the structures of hemes and heme proteins and the functions of heme proteins. This database will provide the structure-function relationships focusing on heme porphyrin distortion and lead to the elucidation of the origin of the functional diversity of heme proteins. In addition, the insights obtained from the database can be used for the design of protein function. PyDISH contains the structural data of more than 13 000 hemes extracted from the Protein Data Bank, including heme porphyrin distortion, axial ligands coordinating to the heme and the orientation of the propionate sidechains of heme. PyDISH also has information about the protein domains, including Uniprot ID, protein fold by CATH ID, organism, coordination distance and so on. The analytical tools implemented in PyDISH allow users to not only browse and download the data but also analyze the structures of heme porphyrin by using the analytical tools implemented in PyDISH. PyDISH users will be able to utilize the obtained results for the design of protein function. Database URL: http://pydish.bio.info.hiroshima-cu.ac.jp/., (© The Author(s) 2020. Published by Oxford University Press.)

A 65-year-old woman with spinocerebellar ataxia presented with generalized seizures due to subcortical hemorrhaging. Magnetic resonance imaging (MRI) revealed obstruction of the superior sagittal sinus. Despite treatment, she became comatose. MRI newly revealed subdural fluid collection and descent of the brainstem. Her history indicated a recent fall, prompting additional studies, which revealed lumbar fracture and cerebrospinal fluid (CSF) leaks. We performed an epidural blood patch, and her consciousness was fully restored in one month. This is the first report of cerebral venous thrombosis with CSF leaks in the lumbar region due to a fall injury.

Objective: Although intravenous indocyanine green (ICG) videoangiography has been reported to be useful when applied to cerebral arteriovenous malformation (AVM) surgery, the ICG that remains after the procedure makes it difficult to understand the anatomy, to evaluate nidus blood flow changes, and to repeat ICG videoangiography within a short time. Intraarterial ICG videoangiography has emerged as a way to overcome these limitations. The current study presents the results of intraarterial ICG videoangiography undertaken in patients with cerebral AVMs., Methods: Intraarterial ICG videoangiography was performed in 13 patients with cerebral AVMs. Routine intraoperative digital subtraction angiography at the authors' institution is performed in a hybrid operating room during AVM surgery and includes the added step of injecting ICG to the contrast medium that is administered through a catheter., Results: Predissection studies were able to visualize the feeder in 12 of 13 cases. The nidus was visualized in 12 of 13 cases, while the drainer was visualized in all cases. After total dissection of the nidus, there was no ICG filling in the drainers found in any of the cases. Washout of the ICG took 4.4 ± 1.3 seconds in the feeders, 9.2 ± 3.5 seconds in the drainers, and 20.9 ± 3.4 seconds in all of the vessels. Nidus flow reduction was confirmed during dissection in 9 of 9 cases. Flow reduction was easy to recognize due to each span being very short. Color-encoded visualization and objective data obtained by Flow 800 analysis reinforced these findings., Conclusions: The results showed that intraarterial ICG videoangiography was more useful than intravenous ICG videoangiography in cerebral AVM surgery. This was especially effective in the identification of the feeder, nidus, and drainer and in the assessment of the flow dynamics of the nidus. Use of Flow 800 made it simpler and easier to evaluate these findings.

Background: Although mechanical thrombectomy is a standard endovascular therapy for patients with acute ischemic stroke (AIS), the incidence of and risk factors for contrast-induced nephropathy (CIN) following mechanical thrombectomy are infrequently reported., Objectives: The aim of this study was to investigate the incidence and risk factors for CIN following mechanical thrombectomy for AIS, and whether the incidence of CIN is related to a poor prognosis., Methods: We examined consecutive patients who underwent a mechanical thrombectomy in the period from January 2014 to March 2018. The patients' clinical backgrounds, treatments, and clinical prognoses were analyzed. CIN was defined as an increase in the serum creatinine level of ≥44.2 μmol/L (0.5 mg/dL) or 25% above baseline within 72 h after exposure to the contrast medium., Results: In total, 80 patients (46 men and 34 women aged 74.5 ± 11.5 years) who met our inclusion criteria were analyzed. CIN occurred in 8.8% (7/80) of the patients following mechanical thrombectomy. Although no patients needed permanent dialysis, 1 required temporary dialysis. The median amount of contrast medium was 109 mL. A comparison between the groups with and without CIN showed a significant difference in white blood cell (WBC) count at the time of admission (11.6 ± 2.7 × 103/μL and 8.1 ± 2.7 × 103/μL; p < 0.01) and the cut-off value was 9.70 × 103/μL. In multivariate analysis, contrast volume/estimated glomerular filtration rate by creatinine and WBC count were significantly associated with the incidence of CIN, with odds ratios of 1.64 (95% CI 1.02-2.65; p = 0.04) and 1.61 (95% CI 1.15-2.25; p < 0.01), respectively., Conclusions: This study found that CIN occurred in 8.8% of patients with AIS following mechanical thrombectomy. High WBC count was associated with an increased risk of CIN and may be helpful for predicting CIN., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Arteriovenous malformations (AVMs) are hemorrhagic vascular diseases in which arteries and veins are directly connected with no capillary bed between the two. We herein introduce the results of basic research of this disease and surgical techniques based on our data and experiences. The results obtained from our research show that cell death- and inflammation-related molecules changed or became activated compared with control specimens. These findings indicate that chronic inflammation occurs in and around the nidus of AVMs. Various molecules are involved in the mechanisms of cell death and angiogenesis during this process. Confirmation of blood flow in the nidus is very important to avoid hemorrhagic complications during surgical removal of the nidus. The risk of hemorrhage increases when the blood flow in the nidus is not reduced. We reported the advantages of serial indocyanine green videoangiography, which is used to assess the blood flow during AVM nidus removal. Since publication of the ARUBA trial and Scottish Audit, treatments with high morbidity have not been allowed. It is especially important for neurosurgeons to treat low Spetzler-Martin grade AVMs with low morbidity. J. Med. Invest. 67 : 222-228, August, 2020.

Purpose: Mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients due to emergent large vessel occlusion (ELVO) is standard treatment, the benefits, however, are highly time-sensitive. After patient eligibility for reperfusion therapy is determined by conventional radiological examinations, the time to be transferred from the department of radiological examination to angiography-suites is critical. We speculated that the time required for the diagnosis of AIS might be reduced if we could determine MT eligibility in patients with ELVO at angiography-suites. Modern angiography-suites with flat panel detectors can perform cone beam (CB)-CT. We performed CB-CTA using intravenous injection of contrast agent to evaluate occlusion sites, collateral score, and construction of vessels distal to occlusion sites and determined if CB-CTA could be useful to evaluate patients with ELVO., Methods: We included 15 patients with ELVO diagnosed by conventional MRI or CT/CTA, and investigated whether CB-CTA was reliable to diagnose occlusion sites. We also studied if collateral score on CB-CTA was associated with prognosis after successful reperfusion by MT by comparison between favorable (modified Rankin scale (mRS) 0-2), and unfavorable outcome group (mRS 3-6)., Results: There was strong agreement of occlusion sites between CB-CTA and conventional radiological examination (κ = 0.80). Collateral score determined by CB-CTA was significantly different between favorable outcome and unfavorable outcome group (median collateral score 2.3 v.s. 1.3, p = 0.040)., Conclusions: Although prospective study of AIS patients at a radiography department is indispensable, CB-CTA performed in an angiography-suite might be useful to evaluate patients with ELVO., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The pathogenesis of intracranial aneurysm rupture remains unclear. Because it is difficult to study the time course of human aneurysms and most unruptured aneurysms are stable, animal models are used to investigate the characteristics of intracranial aneurysms. The authors have newly established a rat intracranial aneurysm rupture model that features site-specific ruptured and unruptured aneurysms. In the present study the authors examined the time course of changes in the vascular morphology to clarify the mechanisms leading to rupture., Methods: Ten-week-old female Sprague-Dawley rats were subjected to hemodynamic changes, hypertension, and ovariectomy. Morphological changes in rupture-prone intracranial arteries were examined under a scanning electron microscope and the association with vascular degradation molecules was investigated., Results: At 2-6 weeks after aneurysm induction, morphological changes and rupture were mainly observed at the posterior cerebral artery; at 7-12 weeks they were seen at the anterior Willis circle including the anterior communicating artery. No aneurysms at the anterior cerebral artery-olfactory artery bifurcation ruptured, suggesting that the inception of morphological changes is site dependent. On week 6, the messenger RNA level of matrix metalloproteinase-9, interleukin-1β, and the ratio of matrix metalloproteinase-9 to the tissue inhibitor of metalloproteinase-2 was significantly higher at the posterior cerebral artery, but not at the anterior communicating artery, of rats with aneurysms than in sham-operated rats. These findings suggest that aneurysm rupture is attributable to significant morphological changes and an increase in degradation molecules., Conclusions: Time-dependent and site-dependent morphological changes and the level of degradation molecules may be indicative of the vulnerability of aneurysms to rupture.

Background: After aneurysmal subarachnoid hemorrhage (aSAH), crystalloid fluids with a relatively high sodium concentration have been used to maintain the cerebral blood flow. However, the prophylactic delivery of water and sodium by intravenous (IV) infusion will not necessarily improve the prognosis of patients after aSAH, and the excessive supply of water and sodium can negatively affect the outcome. We hypothesized that the delivery of an optimal amount of water and sodium separately might improve the outcome after aSAH., Methods: We recruited 55 consecutive patients who had undergone clipping or endovascular coil embolization after aSAH. Group 1 (n = 33) received conventional therapy (i.e., prophylactic IV sodium and water [protocol 1]). Group 2 (n = 22) received the optimal amount of water and sodium separately (protocol 2)., Results: The median total of water and sodium chloride supplied in group 1 was significantly greater than that supplied in group 2 (P < 0.01). The modified Rankin scale score at discharge was 0-2 in 15 patients (95%) in group 2 and 23 patients (55%) in group 1 (P < 0.001). On multivariate logistic regression analysis, the odds ratio for a discharge modified Rankin scale score of 0-2 or 3-6 was significantly associated with the treatment protocol (P < 0.05) and the net fluid balance on days 4-8 (P < 0.05)., Conclusion: The separate delivery of optimal amounts of water and sodium could be a promising therapeutic strategy to improve the prognosis after aSAH., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Carotid endarterectomy (CEA) is widely used for cervical artery stenosis. In Japan, primary closure after endarterectomy has been a standard technique. Recently, the patch closure has been shown to be superior to the primary suture for the prevention of restenosis and ipsilateral stroke. This study evaluated the 5- and 10-year outcomes following CEA with patch graft closure in our institution. Between January 2000 and March 2013, 134 patients, who underwent CEA with patch graft closure were investigated in the current retrospective study. Among these patients, 102 CEAs in 97 patients were followed up for 5 years and 66 CEAs in 61 patients were for 10 years after the procedure. Restenosis was defined as >50% recurrent luminal narrowing at the endarterectomy site. In 5 years, symptomatic restenosis exhibited minor stroke in one patient at 58 months after CEA (restenosis rate 1.0%). The ipsilateral minor stroke occurred in three patients including the above case (2.9%). In 10 years, asymptomatic restenosis occurred in three patients in addition to the above symptomatic case (restenosis rate 6.1%), and the ipsilateral minor stroke occurred in four patients (6.1%). Carotid endarterectomy with patch graft exerted a high protective effect from restenosis up to 5 and 10 years in our institution. The number of carotid artery stenting is increasing all over the world but we speculated that the established surgical procedure of patched CEA prevented restenosis and ipsilateral stroke.

Background: Mechanical thrombectomy undoubtedly improves functional outcomes for patients with acute ischemic stroke. Although we have observed occlusion sites that protrude proximally into the vessel on angiography, termed the "claw sign," we have been unable to state its clinical significance. In this study, we aimed to determine whether the presence of a claw sign was related to recanalization success after mechanical thrombectomy., Materials and Methods: We retrospectively included 73 consecutive patients treated for acute cerebral large vessel occlusion by mechanical thrombectomy between January 2014 and December 2017. The angiographic claw sign was defined as a thrombus that protruded proximally by more than half the diameter of the parent artery. Claw sign positivity, clinical and etiological features, and outcomes were compared between groups with and without recanalization., Results: The claw sign was observed in 29 of 73 (40%) patients and was positive significantly more frequently in those with recanalization (50.0%) than in those without recanalization (5.9%) (P < .01). By multivariate analysis, the claw sign was the only pretreatment parameter to predict successful recanalization (odds ratio, 12.50; 95% confidence interval, 1.50-103.00; P = .019)., Conclusions: The presence of the claw sign might predict successful recanalization in patients undergoing mechanical thrombectomy for large vessel occlusion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The observation of walking improves gait ability in chronic stroke survivors. It has also been suggested that activation of the mirror neuron system contributes to this effect. However, activation of the mirror neuron system during gait observation has not yet been assessed in sub-acute stroke patients. The objective of this study was to clarify the activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons. In this study, we sequentially enrolled five sub-acute stroke patients who had undergone gait training and nine healthy persons. We used fMRI to detect neuronal activation during gait observation. During the observation period in the stroke group, neural activity in the left inferior parietal lobule, right and left inferior frontal gyrus was significantly higher than during the rest period. In the healthy group, neural activity in the left inferior parietal lobule, left inferior frontal gyrus, left middle frontal gyrus, left superior temporal lobule and right and left middle temporal gyrus was significantly higher than during the rest period. The results indicate that the mirror neuron system was activated during gait observation in sub-acute stroke patients who had undergone gait training and also in healthy persons. Our findings suggest that gait observation treatment may provide a promising therapeutic strategy in sub-acute stroke patients who have experienced gait training., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

An arteriovenous fistula of the superficial temporal artery (STA) is a direct and abnormal communication between the STA, feeding artery, and superficial temporal vein, draining veins that bypass the capillary network. Several cases of trauma-induced or iatrogenic-induced arteriovenous fistula (AVF) of the STA have been reported ; however, spontaneous AVF of the STA not associated with trauma or medical treatment are extremely rare. Herein, we present a case of spontaneous AVF of the STA diagnosed in old age. J. Med. Invest. 66 : 209-210, February, 2019.

Background and Purpose: Little attention has been paid to the pathogenesis of in-hospital stroke, despite poor outcomes and a longer time from stroke onset to treatment. We studied the pathophysiology and biomarkers for detecting patients who progress to in-hospital ischemic stroke (IHS)., Methods: Seventy-nine patients with IHS were sequentially recruited in the period 2011-2017. Their characteristics, care, and outcomes were compared with 933 patients who had an out-of-hospital ischemic stroke (OHS) using a prospectively collected database of the Tokushima University Stroke Registry., Results: Active cancer and coronary artery disease were more prevalent in patients with IHS than in those with OHS (53.2 and 27.8% vs. 2.0 and 10.9%, respectively; p < 0.001), the median onset-to-evaluation time was longer (300 vs. 240 min; p = 0.015), and the undetermined etiology was significantly higher (36.7 vs. 2.4%; p < 0.001). Although there was no significant difference in stroke severity at onset between the groups, patients with IHS had higher modified Rankin Scale (mRS) scores (3-6) at discharge (67.1 vs. 50.3%; p = 0.004) and rates of death during hospitalization (16.5 vs. 2.9%; p < 0.001). D-dimer (5.8 vs. 0.8 µg/mL; p < 0.001) and fibrinogen (532 vs. 430 mg/dL; p = 0.014) plasma levels at the time of onset were significantly higher in patients with IHS after propensity score matching. Multivariate logistic regression analysis revealed that active cancer (odds ratio [OR] 2.30; 95% confidence interval [CI] 1.26-4.20), prestroke mRS scores 3-5 (OR 6.78; 95% CI 3.96-11.61), female sex (OR 1.57; 95% CI 1.19-2.08), and age ≥75 years (OR 2.36; 95% CI 1.80-3.08) were associated with poor outcomes., Conclusions: Patients with IHS had poorer outcomes than those with OHS because of a higher prevalence of active cancer and functional dependence before stroke onset. Elevated plasma levels of D-dimer and fibrinogen, especially with active cancer, can help identify patients who are at a higher risk of progression to IHS., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

We conducted a retrospective study to investigate adverse drug reactions and associated medical costs among elderly individuals that could be avoided if pharmacotherapy was performed in accordance with the Beers Criteria: the Japanese Version (BCJV) and Guidelines for Medical Treatment and Its Safety in the Elderly 2015 (GL2015). Patients aged at least 65 years who were either hospitalized at Gifu Municipal Hospital between October 1 and November 30, 2014 (n = 1236) or had outpatient examinations at Gifu Municipal Hospital on October 1-2, 2014 (n = 980) were included in the study. The outcomes measured were usage rates of drugs listed in the BCJV and GL2015, incidence rates of adverse drug reactions, and additional costs incurred per patient due to adverse reactions. Among the inpatients, usage rates of drugs listed in the BCJV and GL2015 were 24.0 and 72.4%, respectively, and adverse reactions to these drugs occurred at rates of 3.0 and 8.2%, respectively. Among the outpatients, while the usage rates were 26.2% (BCJV) and 59.9% (GL2015), the incidence rates of adverse reactions were 4.7% (BCJV) and 3.9% (GL2015). The additional costs incurred due to adverse drug reactions ranged from 12713-163925 yen per patient. Our results demonstrate that appropriate use of drugs based on the BCJV and GL2015 can help prevent adverse reactions; this would reduce the overall medical costs.