Cerebral Small Vessel Disease Burden for Bleeding Risk during Antithrombotic Therapy: Bleeding with Antithrombotic Therapy 2 Study.

OBJECTIVE: This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden. METHODS: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events. RESULTS: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1-3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26-13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99-43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08-2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13-10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02-6.35) significantly increased in SVD score 4 compared to score 0. INTERPRETATION: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774-787.

Sequential detection rates of intramural hematoma for diagnosing spontaneous intracranial artery dissection.

BACKGROUND AND PURPOSE: Spontaneous intracranial artery dissection (IAD) can be definitively diagnosed by detecting intramural hematoma (IMH) on arterial wall imaging. However, evidence of a time-dependent natural history for the development of radiological findings is lacking. Therefore, this study aimed to determine when imaging detects IAD. METHODS: We obtained data from our cohort databases between March 2011 and August 2018 on consecutive patients who had definite, probable, or possible IAD based on the multidisciplinary expert consensus criteria. We assessed IMH on initial and follow-up high-resolution three-dimensional T1-weighted imaging (HR-3D-T1WI). We retrospectively investigated the association between IMH detection and days from symptom onset to initial HR-3D-T1WI and compared the IMH detection rate with other definitive diagnostic arterial dissection findings. RESULTS: We analyzed 106 patients (mean age = 51 ± 13 years, 31 women) with at least initial HR-3D-T1WI data. The final diagnoses were definite, probable, and possible IAD in 83, 18, and 5 patients, respectively. IMHs were observed in 63 patients (59%, 95% confidence interval [CI] = 49%-69%). Overall IMH detection rate was 55% (95% CI = 45%-64%), 20% (95% CI = 3%-60%), 40% (95% CI = 21%-64%), and 50% (95% CI = 37%-63%) on the initial HR-3D-T1WI and Days 3, 7, and 13, respectively. Among 68 patients evaluated with digital subtraction angiography and HR-3D-T1WI, IMH was confirmed more frequently than other definitive diagnostic arterial dissection findings. CONCLUSIONS: The overall IMH detection rate on HR-3D-T1WI was >50% and peaked in 1-2 weeks. IMH was a frequently detectable finding for the diagnosis of IAD compared to other radiological findings.

Relationship between a deep learning model and liquid-based cytological processing techniques.

OBJECTIVE: Artificial intelligence (AI)-based cytopathology studies conducted using deep learning have enabled cell detection and classification. Liquid-based cytology (LBC) has facilitated the standardisation of specimen preparation; however, cytomorphology varies according to the LBC processing technique used. In this study, we elucidated the relationship between two LBC techniques and cell detection and classification using a deep learning model. METHODS: Cytological specimens were prepared using the ThinPrep and SurePath methods. The accuracy of cell detection and cell classification was examined using the one- and five-cell models, which were trained with one and five cell types, respectively. RESULTS: When the same LBC processing techniques were used for the training and detection preparations, the cell detection and classification rates were high. The model trained on ThinPrep preparations was more accurate than that trained on SurePath. When the preparation types used for training and detection were different, the accuracy of cell detection and classification was significantly reduced (P < 0.01). The model trained on both ThinPrep and SurePath preparations exhibited slightly reduced cell detection and classification rates but was highly accurate. CONCLUSIONS: For the two LBC processing techniques, cytomorphology varied according to cell type; this difference affects the accuracy of cell detection and classification by deep learning. Therefore, for highly accurate cell detection and classification using AI, the same processing technique must be used for both training and detection. Our assessment also suggests that a deep learning model should be constructed using specimens prepared via a variety of processing techniques to construct a globally applicable AI model.

A safe and sustainable bacterial cellulose nanofiber separator for lithium rechargeable batteries.

Bacterial cellulose nanofiber (BCNF) with high thermal stability produced by an ecofriendly process has emerged as a promising solution to realize safe and sustainable materials in the large-scale battery. However, an understanding of the actual thermal behavior of the BCNF in the full-cell battery has been lacking, and the yield is still limited for commercialization. Here, we report the entire process of BCNF production and battery manufacture. We systematically constructed a strain with the highest yield (31.5%) by increasing metabolic flux and improved safety by introducing a Lewis base to overcome thermochemical degradation in the battery. This report will open ways of exploiting the BCNF as a "single-layer" separator, a good alternative to the existing chemical-derived one, and thus can greatly contribute to solving the environmental and safety issues.

Presence of Sarcocystis sybillensis in Japanese sika deer (Cervus nippon) captured in its native territory and its phylogenetic relationship with Sarcocystis nipponi.

The first study reporting the morphological characterization of Sarcocystis sybillensis was performed in 1983; however, without any molecular analysis. Sarcocystis nipponi has been recently described as a species synonymic to S. sybillensis. We reconfirmed the presence of S. sybillensis in Japanese sika deer (Cervus nippon) captured in its native territory; and performed its molecular and phylogenetic characterization. The morphological characteristics of the sarcocysts were consistent with those of S. nipponi and S. sybillensis described in the first report. However, the nucleotide sequence of 18S rRNA gene of S. sybillensis showed only 91.9% identity to that of S. nipponi, suggesting low homology among the concerned Sarcocystis spp. Accordingly, S. sybillensis was found to occupy a clade distinct from that of S. nipponi in a phylogenetic tree of Sarcocystis. Therefore, the present study provides essential information on 18S rRNA-based molecular characterization of S. sybillensis and disproves the existing notion of morphology-based species synonymity of S. sibillensis and S. nipponi. These results also suggest that S. sybillensis belongs to type 2 Sarcocystis.

Strain-Dependent Prion Infection in Mice Expressing Prion Protein with Deletion of Central Residues 91-106.

Conformational conversion of the cellular prion protein, PrPC, into the abnormally folded isoform, PrPSc, is a key pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Transgenic mice expressing PrP with a deletion of the central residues 91-106 were generated in the absence of endogenous PrPC, designated Tg(PrP∆91-106)/Prnp0/0 mice and intracerebrally inoculated with various prions. Tg(PrP∆91-106)/Prnp0/0 mice were resistant to RML, 22L and FK-1 prions, neither producing PrPSc∆91-106 or prions in the brain nor developing disease after inoculation. However, they remained marginally susceptible to bovine spongiform encephalopathy (BSE) prions, developing disease after elongated incubation times and accumulating PrPSc∆91-106 and prions in the brain after inoculation with BSE prions. Recombinant PrP∆91-104 converted into PrPSc∆91-104 after incubation with BSE-PrPSc-prions but not with RML- and 22L-PrPSc-prions, in a protein misfolding cyclic amplification assay. However, digitonin and heparin stimulated the conversion of PrP∆91-104 into PrPSc∆91-104 even after incubation with RML- and 22L-PrPSc-prions. These results suggest that residues 91-106 or 91-104 of PrPC are crucially involved in prion pathogenesis in a strain-dependent manner and may play a similar role to digitonin and heparin in the conversion of PrPC into PrPSc.

Associations of High Intensities on Magnetization-Prepared Rapid Acquisition with Gradient Echo with Aortic Complicated Lesions in Ischemic Stroke Patients.

BACKGROUND: Aortic complicated lesions (ACLs) are key parameters for evaluating aortic embolic sources in embolic stroke, and are usually diagnosed using transesophageal echocardiography (TEE). However, alternative methods for diagnosing ACLs have not been well established. We investigated associations between high-intensity areas on T1-weighted imaging (T1WI) with magnetization-prepared rapid acquisition with gradient echo (MPRAGE) and ACLs on TEE among ischemic stroke patients. METHODS: Participants comprised 135 patients (mean age, 71 years; 35 women) with ischemic stroke or transient ischemic attack who underwent TEE for evaluation of embolic sources and plaque imaging using MPRAGE for evaluation of aortic or carotid plaques. Aortic plaque with signal intensity ≥200% of sternocleidomastoid intensity on MPRAGE was categorized as "high intensity". ACLs on TEE were defined by focal increases in intima-media thickness (IMT) ≥4.0 mm or the presence of ulcerated or mobile plaques. RESULTS: Fifty-six patients (42%) showed high-intensity areas on MPRAGE at the aortic arch. Aortic maximum IMT was significantly higher in patients with high intensities than in those without (p < 0.001). Incidences of ACLs (66 vs. 20%, p < 0.001) or ulcerated or mobile plaques (30 vs. 6%, p < 0.001) were significantly higher in patients with high intensities than in patients without. Multivariable logistic regression analysis showed that high intensities on MPRAGE were independently associated with the presence of ACLs (OR 5.72; 95% CI 2.38-13.70) and ulcerated or mobile plaques (OR 4.18; 95% CI 1.29-13.50). CONCLUSIONS: High intensities on T1WI with MPRAGE in the aortic arch were significantly associated with the presence of ACLs. An evaluation of the aortic arch using MPRAGE may be useful for predicting ACLs.

Clinical and Radiological Characteristics of Intracranial Artery Dissection Using Recently Proposed Diagnostic Criteria.

BACKGROUND: Data on the clinical and radiological characteristics of intracranial artery dissection (IAD) have remained limited. Our purpose was to reveal the clinical and radiological characteristics of IAD according to diagnostic criteria for IAD as recently reported by a group of international experts. METHODS: Patients were retrospectively enrolled using a prospective single-center stroke registry between 2011 and 2016. Baseline characteristics and radiological findings including conventional magnetic resonance imaging (MRI) sequences, magnetic resonance angiography (MRA), high-resolution 3-dimensional T1-weighted imaging (HR-3D-T1WI), and digital subtraction angiography were reviewed. We performed statistical comparisons to determine which findings from which modalities are useful. RESULTS: We identified 118 patients with suspected artery dissection, with 64 patients (median age, 51 [interquartile range, 45-56) years; 16 women) finally meeting the criteria for definite (n = 47), probable (n = 15), or possible (n = 2) idiopathic IAD. Ischemic stroke alone was found in 31 patients (48%) on admission. There were 36 patients (56%) suffering from hypertension and 39 (61%) with smoking history. The vertebral artery alone was the most affected in 42 patients (66%). Intramural hematoma (IMH) was more frequently detected on HR-3D-T1WI than on conventional MRI/MRA (odds ratio, 4.72; 95% confidence interval, 1.71-13.00). In 54 patients (84%), the modified Rankin Scale score after 3 months was 0-1. CONCLUSIONS: Male dominance and age at IAD onset were similar to previous studies, and more than half had hypertension and smoking history. We confirmed that HR-3D-T1WI is useful for detecting IMH in the diagnostic criteria.

Detection of Stenosis Progression in Intracranial Vertebral Artery Dissection Using Carotid Ultrasonography.

BACKGROUND: The purpose of this study was to assess whether carotid ultrasonography indices detect arterial stenosis progression in patients with vertebral artery (VA) dissection. METHODS: This was a retrospective, single-center, observational study that enrolled patients with intracranial VA dissection who were admitted from January 2011 to June 2017. Magnetic resonance angiography (MRA) was done on admission and followed up at a median 20 days after onset (interquartile range [IQR] 9-58 days), and ultrasonography was performed at a median of 22 (interquartile range 7-56) days. Peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV), and pulsatility index (PI) were measured by ultrasonography, and the ratio of each follow-up value to the baseline (follow-up/baseline) value was calculated. Two stroke neurologists categorized into 3 groups by morphological changes of the dissected vessel: patients with stenosis progression (progression group: P-group); those with no remarkable change or dilatation improved (stable group: S-group); and those with stenosis regression or dilatation enlargement (enlargement group: E-group). Ultrasonography indices were compared among the groups. RESULTS: Of the 42 patients who were enrolled to this study, 39 patients underwent ultrasonography and MRA on both admission and follow-up. The PI ratio was significantly higher in the P-group than in the S-group (1.96 ± .80 versus .98 ± .44, P = .02) and in the E-group (versus .65 ± .35, P < .01). There were no significant differences in the PSV ratio, EDV ratio, and MV ratio. CONCLUSIONS: In patients with VA dissection, the PI ratio on ultrasonography is a promising index to detect stenosis progression.

Cross-Coupling Reaction of Allylic Ethers with Aryl Grignard Reagents Catalyzed by a Nickel Pincer Complex.

A cross-coupling reaction of allylic aryl ethers with arylmagnesium reagents was investigated using ß-aminoketonato- and ß-diketiminato-based pincer-type nickel(II) complexes as catalysts. An ß-aminoketonato nickel(II) complex bearing a diphenylphosphino group as a third donor effectively catalyzed the reaction to afford the target cross-coupled products, allylbenzene derivatives, in high yield. The regioselective reaction of a variety of substituted cinnamyl ethers proceeded to give the corresponding linear products. In contrast, α- and γ-alkyl substituted allylic ethers afforded a mixture of the linear and branched products. These results indicated that the coupling reaction proceeded via a π-allyl nickel intermediate.

Flip-Flop Phenomenon: Swallowing-Induced Arterial Displacement as an Indicator of Carotid Artery Disease.

BACKGROUND AND PURPOSE: The dynamic displacement of the carotid arteries with interference of the hyoid bone during swallowing, named as "flip-flop" phenomenon (FFP), may be associated with ischemic stroke. However, the extent to which FFP is prevalent in carotid artery disease remains unknown. We aimed to investigate its exact prevalence to explore the relationship between FFP and carotid artery disease. METHODS: We examined 202 consecutive patients who were affected by neurological diseases including cerebrovascular diseases. Using carotid ultrasound, we evaluated carotid intima-media thickness, internal carotid artery stenosis (ICS), and FFP during swallowing with neck rotation. RESULTS: FFP was observed in 39 of the 202 patients (19.3%). Patients with FFP showed significantly higher prevalence of ICS than those without FFP (12/39 [30.8] vs. 21/163 [12.9%]; p = 0.007). Among those with ICS (n = 33; 36 vessels), FFP was associated with symptomatic ICS more frequently than with asymptomatic ICS (6/11 [54.5] vs. 5/25 [20.0%]; p = 0.038). Among those with unilateral FFP (n = 37), the prevalence of ipsilateral ICS was higher than that of contralateral ICS (9/37 [24.3] vs. 2/37 [5.4%]; p = 0.035). CONCLUSIONS: FFP accompanies the swallowing movement in some neurological patients, and more frequently in patients with ICS. FFP may thus be a novel indicator of stroke.

Early Achievement of Blood Pressure Lowering and Hematoma Growth in Acute Intracerebral Hemorrhage: Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study.

BACKGROUND: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. METHODS: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg. RESULTS: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038-0.867; p = 0.032). CONCLUSIONS: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH.

High-sensitivity sulfur isotopic measurements for Antarctic ice core analyses.

RATIONALE: Sulfur is widely distributed in nature, and sulfur isotopic measurements have been applied to elucidate the origin and transport of sulfuric compounds in the lithosphere, biosphere, and atmosphere. Analyses of samples containing small amounts of sulfur, such as the Antarctic ice core samples analyzed herein, require a high-sensitivity analytical method. METHODS: We developed a high-sensitivity sulfur isotopic ratio (δ34 S value) analytical system equipped with an elemental analyzer, a cryo-flow device, and an isotope ratio mass spectrometer, and established a measurement and calibration procedure. RESULTS: Using this system, we precisely measured the δ34 S values of samples containing 5-40 nmol sulfate. Test runs were performed on samples from the Antarctic shallow ice core DF01, and the data obtained were consistent with those obtained by previous studies that reported δ34 S values for Antarctic snow and ice samples of more than 200 g (containing more than 150 nmol sulfate). Among the analyzed samples, one showed a peak sulfate concentration in its depth profile that is considered to have resulted from a large volcanic eruption. The δ34 S value obtained at that depth in the sample was distinct from values at other depths and consistent with reported values for volcanic sulfates. CONCLUSIONS: The analytical system developed herein is a powerful tool for trace sulfur isotopic analyses. The results obtained from the DF01 ice core samples are the first step towards elucidating high-time-resolution (less than 1 year) paleo-environmental changes by sulfur isotopic analyses.

Two-Year Outcomes of Anticoagulation for Acute Ischemic Stroke With Nonvalvular Atrial Fibrillation　- SAMURAI-NVAF Study.

BACKGROUND: We determined the 2-year long-term risk-benefit profile in patients with stroke or transient ischemic attack (TIA) receiving warfarin or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry in Japan.Methods and Results:NVAF patients within 7 days after onset of ischemic stroke/TIA were enrolled in 18 stroke centers. Outcome measures included ischemic and bleeding events and death in the 2-year follow-up period. We enrolled 1,116 patients taking either warfarin (650 patients) or DOACs (466 patients) at acute hospital discharge. DOAC users were younger and had lower National Institutes of Health Stroke Scale, CHADS2and discharge modified Rankin Scale scores than warfarin users (P<0.0001 each). Incidences of stroke/systemic embolism (adjusted hazard ratio, 1.07; 95% CI, 0.66-1.72), all ischemic events (1.13; 0.72-1.75), and ischemic stroke/TIA (1.58; 0.95-2.62) were similar between groups. Risks of intracranial hemorrhage (0.32; 0.09-0.97) and death (0.41; 0.26-0.63) were significantly lower for DOAC users. Infection was the leading cause of death, accounting for 40% of deaths among warfarin users. CONCLUSIONS: Stroke/TIA patients receiving DOACs for secondary prevention were younger and had lower stroke severity and risk indices than those receiving warfarin. Estimated cumulative incidences of stroke and systemic embolism within 2 years were similar between warfarin and DOACs users, but those of death and intracranial hemorrhage were significantly lower among DOAC users.

Embolic Stroke due to Carotidynia Potentially Associated with Moving Carotid Artery Caused by Swallowing.

A 63-year-old woman with end-stage renal disease on maintenance hemodialysis discontinued her medication for rheumatoid arthritis with prednisolone and azathioprine. One month later, she was admitted because of consciousness disturbance and right hemiparesis. Diffusion-weighted brain magnetic resonance imaging (MRI) revealed multiple hyperintensities in her left frontal and parietal lobes. She also developed high fever and left neck pain. Carotid ultrasonography showed calcified plaque with vessel wall swelling at the bifurcation of the left common carotid artery (LCCA) and surrounding hypoechoic soft tissue. The tissue was identified as an isodense lesion on noncontrast computed tomography (CT) and as a high-intensity lesion on fat-saturated T2-weighted MRI. From her symptoms and radiological findings, she was diagnosed with carotidynia. Cervical MRI also showed that the LCCA was transposed to a retropharyngeal location, suggesting a moving carotid artery. Carotid ultrasonography revealed that the LCCA moved to and from the retropharyngeal position with swallowing and was thus being compressed by the hyoid bone. After corticosteroid therapy was initiated with 30 mg of prednisolone, her symptoms and radiological findings improved. To our knowledge, this is the first report of a case of cerebral embolism due to carotidynia. The repetitive compressions by the hyoid bone during swallowing were presumed to have provoked shear stress and inflammation of the carotid vessel wall, which was aggravated by discontinuation of steroid therapy in our case. These mechanical and inflammatory stresses might cause dysfunction of endothelial cells, hypercoagulation, platelet hyperaggregation, and vulnerability and rupture of carotid plaques, and may subsequently result in embolic strokes.

A Novel Evaluation for Predicting Aortic Complicated Lesions Using Calcification on Chest X-ray.

BACKGROUND: The aorta is a significant source of cerebral thromboembolisms. Aortic complicated lesions (ACLs) are key findings on transesophageal echocardiography (TEE) for assessing aortic sources of emboli to the brain. TEE is sometimes avoided due to its invasiveness. However, few reports have examined alternative methods for predicting ACLs. We investigated relationships between aortic arch calcification (AAC) on chest X-ray and ACLs. METHODS: Participants comprised 300 patients with acute ischemic stroke or transient ischemic attack who underwent TEE for the evaluation of the aortic arch and heart. A postero-anterior plain chest X-ray in the recumbent position was evaluated on admission for each patient. AAC was evaluated using 4 grades (0-3) and "AAC thickness" defined as the distance from the inner margin of the most distant AAC to the outer margin of the aortic vessel wall. ACLs were defined by intima-media thickness (IMT) ≥4.0 mm or presence of ulcerated or mobile plaques. Carotid maximum IMT on ultrasonography was also evaluated. Comparison of the diagnostic ability to predict ACL was performed between AAC grades and AAC thickness or AAC thickness and carotid maximum IMT using the Delong method. RESULTS: ACLs were identified in 71 patients (23.7%), including ACLs with ulcerated plaques in 24 (8.0%) and ACLs with mobile plaques in 9 (3.0%). Plaque thickness was greater in higher AAC grades or higher quartiles of AAC thickness (p for trend <0.001 each). The Cochran-Armitage test showed that both higher AAC grade and higher quartile of AAC thickness were significantly associated with the presence of ACLs, as well as the presence of ulcerated or mobile plaques (p for trend < 0.001 each). Receiver-operating characteristic (ROC) analysis showed optimal cut-off values for AAC thickness of 5.6 mm for ACLs and 6.0 mm for ulcerated or mobile plaques. Multivariate logistic regression revealed a higher grade of AAC (grades 2-3) and AAC thickness (≥6 mm) as significantly associated with ACLs and ulcerated or mobile plaques (p < 0.001 each). ROC curve comparisons showed that AAC thickness offered a better marker of ACLs than AAC grade (p = 0.019), although no significant difference was evident between AAC thickness and carotid maximum IMT (p = 0.567). CONCLUSIONS: AAC on chest X-ray, evaluated by both AAC grade and AAC thickness to the outer aortic vessel wall, was significantly associated with ACLs on TEE. AAC thickness was suggested as more useful than AAC grade and equivalent to carotid IMT in predicting ACLs.

Non-Hypervascular Hypointense Hepatic Nodules during the Hepatobiliary Phase of Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI as a Risk Factor of Intrahepatic Distant Recurrence after Radiofrequency Ablation of Hepatocellular Carcinoma.

BACKGROUND: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI have been reported to be associated with intrahepatic distant recurrence (IDR) after hepatectomy or radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). IDR is categorized into hypervascular transformation of non-hypervascular hypointense hepatic nodules and new intrahepatic recurrence. The aim of this study was to evaluate the relationship between non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA-enhanced MRI and IDR after RFA, focusing on new intrahepatic recurrence. METHODS: Ninety-one consecutive patients with 115 HCCs undergoing pretreatment Gd-EOB-DTPA-enhanced MRI and RFA for treatment of HCC were enrolled. RESULTS: Of the 91 patients who underwent RFA for HCC, 24 had non-hypervascular hypointense hepatic nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrences were observed in 15 and 19 patients with and without non-hypervascular hypointense hepatic nodules, respectively. Of the 15 recurrences in patients with non-hypervascular hypointense hepatic nodules, 10 patients had new intrahepatic recurrences. The cumulative incidence of new intrahepatic recurrence was significantly higher in patients with non-hypervascular hypointense hepatic nodules than in those without non-hypervascular hypointense hepatic nodules (p < 0.0001). Multivariate analysis revealed that the presence of non-hypervascular hypointense hepatic nodules and Child-Pugh score were independent risk factors for new intrahepatic recurrence. CONCLUSIONS: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were a useful predictive factor for IDR, particularly for new intrahepatic recurrence, after RFA.

As, Cd and Hg in the organs of Todarodes pacificus, Sepia longipes and Sepia madokai in the East China Sea.

Arsenic and Cadmium concentrations in Todarodes pacificus (4 males and 4 females), Sepia longipes (1 male and 3 unknown), five Sepia madokai caught in 2012 (1 male and 4 females) and five S. madokai caught in 2014 (5 females) were collected from the East China Sea (ECS) during intervals from 2010 Oct. through to 2014 Oct. The internal organs were vacuum dried and the elements were measured by ICP-MS. Among the toxic elements, As, Cd, and Hg in the digestive gland, gonads and branchial hearts of squids and cuttlefishes were measured separately. The squid T. pacificus practically inhabits offshore, whereas cuttlefishes, such as S. longipes and S. madokai, inhabit bottom coastal waters in the ECS. Cd concentration in digestive gland of T. pacificus and S. madokai is higher than similar species from other regions. This high concentration seems to be derived from anthropogenic activities and geological conditions present in the ECS. The squid and cuttlefish also accumulate high amounts of As, not only in their digestive gland but also in other organs. Arsenic could be derived from high volcanic activities. In the case of Hg, the muscles were reported to contain the highest concentration in the species studied, but unlike concentration of Cd in digestive gland, it was high compared to other studies. These elements can be utilized as indicators for environmental pollution in marine systems. For monitoring of harmful elements in squids and cuttlefish, for example Cd and As in the digestive gland and Hg in mantle should be measured.

Comparison of Contrast-Enhanced Ultrasound and Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI for the Diagnosis of Macroscopic Type of Hepatocellular Carcinoma.

OBJECTIVE: We compared the efficacy of contrast-enhanced ultrasound sonography (CEUS) with sonazoid and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI for the assessment of macroscopic classification of nodular hepatocellular carcinoma (HCC). METHODS: Seventy-seven consecutive patients with 79 surgically resected HCCs who underwent both preoperative CEUS and Gd-EOB-DTPA-enhanced MRI were enrolled in this retrospective study. Based on the macroscopic diagnosis of resected specimens, nodules were categorized into the simple nodular (SN) and non-SN type HCC. Two hepatologists independently assessed image datasets of the post-vascular phase of CEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI to compare their diagnostic performance. RESULTS: Gd-EOB-DTPA-enhanced MRI enabled the evaluation of macroscopic classification in a significantly larger number of nodules than CEUS (78/79 (98.7%) vs. 70/79 (88.6%), p < 0.05). Of 70 nodules that could be evaluated by both modalities, 41 and 29 nodules were pathologically categorized as SN and non-SN, respectively. The areas under the receiver operating characteristic curve (AUC) for non-SN did not differ between CEUS and Gd-EOB-DTPA-enhanced MRI (reader 1: 0.748 for CEUS, 0.808 for MRI; reader 2: 0.759 for CEUS, 0.787 for MRI). The AUC of combined CEUS and Gd-EOB-DTPA-enhanced MRI for SN HCC was 0.855 (reader 1) and 0.824 (reader 2), indicating higher AUC values for the combined modalities. CONCLUSIONS: The diagnostic performance for macroscopic classification of nodular HCC of CEUS was comparable with that of Gd-EOB-DTPA-enhanced MRI, although some HCCs could not be evaluated by CEUS owing to lower detectability. The combination of the 2 modalities had a more accurate diagnostic performance.

In vitro inhibition and enhancement of liver microsomal S-777469 metabolism by long-chain fatty acids and serum albumin: insight into in vitro and in vivo discrepancy of metabolite formation in humans.

1. It was previously demonstrated that 10% of S-777469, a cannabinoid receptor 2 selective agonist, is metabolized to its carboxylic acid metabolite (S-777469 5-carboxylic acid, 5-CA) in humans in vivo, while the formation of 5-CA is extremely low in human cryopreserved hepatocytes and liver microsomes (HLMs). In this study, factors causing the different metabolite formation rates of S-777469 in vitro and in vivo were investigated. 2. Formation of 5-CA and S-777469 5-hydroxymethyl (5-HM), a precursor metabolite of 5-CA, was catalyzed by CYP2C9. Arachidonic acid, α-linolenic acid, oleic acid and myristic acid, which have been reported to exist in liver microsomes, inhibited S-777469 oxidation by CYP2C9, but serum albumin enhanced this reactions. 3. The IC50 values of these fatty acids for 5-CA formation from 5-HM were lower than those of 5-HM formation from S-777469. Serum albumin extensively enhanced 5-CA formation from 5-HM in comparison to 5-HM formation from S-777469. 4. CYP2C9 was the enzyme responsible for S-777469 oxidation in human livers. The suppressive effects of several fatty acids and enhancing action of serum albumin in vitro are likely to be the causal factors for the apparently different rates of in vitro and in vivo metabolite formation of S-777469.