The influence of contralateral circulation on computational fluid dynamics of intracranial arteries: simulated versus measured flow velocities.

BACKGROUND: This study aimed to retrospectively evaluate the influence of contralateral anterior circulation on computational fluid dynamics (CFD) of intracranial arteries, by comparing the CFD values of flow velocities in unilateral anterior circulation with the measured values from phase-contrast magnetic resonance angiography (PC-MRA). METHODS: We analyzed 21 unilateral anterior circulation models without proximal stenosis from 15 patients who performed both time-of-flight MRA (TOF-MRA) and PC-MRA. CFD was performed with the inflow boundary condition of a pulsatile flow of the internal carotid artery (ICA) obtained from PC-MRA. The outflow boundary condition was given as atmospheric pressure. Simulated flow velocities of the middle cerebral artery (MCA) and anterior cerebral artery (ACA) from CFD were compared with the measured values from PC-MRA. RESULTS: The velocities of MCA were shown to be more accurately simulated on CFD than those of ACA (Spearman correlation coefficient 0.773 and 0.282, respectively). In four models with severe stenosis or occlusion of the contralateral ICA, the CFD values of ACA velocities were significantly lower (< 50%) than those measured with PC-MRA. ACA velocities were relatively accurately simulated in the models including similar diameters of both ACAs. CONCLUSION: It may be necessary to consider the flow condition of the contralateral anterior circulation in CFD of intracranial arteries, especially in the ACA. RELEVANCE STATEMENT: Incorporating the flow conditions of the contralateral circulation is of clinical importance for an accurate prediction of a rupture risk in Acom aneurysms as the bidirectional flow and accurate velocity of both ACAs can significantly impact the CFD results. KEY POINTS: • CFD simulations using unilateral vascular models were relatively accurate for MCA. • Contralateral ICA steno-occlusion resulted in an underestimation of CFD velocity in ACA. • Contralateral flow may need to be considered in CFD simulations of ACA.

Dual-energy computed tomography material decomposition improves prediction accuracy of hematoma expansion in traumatic intracranial hemorrhage.

OBJECTIVE: The angiographic spot sign (AS) on CT angiography (CTA) is known to be useful for predicting expansion in intracranial hemorrhage, but its use is limited due to its relatively low sensitivity. Recently, dual-energy computed tomography (DECT) has been shown to be superior in distinguishing between hemorrhage and iodine. This study aimed to evaluate the diagnostic performance of hematoma expansion (HE) using DECT AS in traumatic intracranial hemorrhage. METHODS: We recruited participants with intracranial hemorrhage confirmed via CTA for suspected traumatic cerebrovascular injuries. We evaluated AS on both conventional-like and fusion images of DECT. AS is grouped into three categories: intralesional enhancement without change, delayed enhancement (DE), and growing contrast leakage (GL). HE was evaluated by measuring hematoma size on DECT and follow-up CT. Logistic regression analysis was used to evaluate whether AS on fusion images was a significant risk factor for HE. Diagnostic accuracy was calculated, and the results from conventional-like and fusion images were compared. RESULTS: Thirty-nine hematomas in 24 patients were included in this study. Of these, 18 hematomas in 13 patients showed expansion on follow-up CT. Among the expanders, AS and GL on fusion images were noted in 13 and 5 hematomas, respectively. In non-expanders, 10 and 1 hematoma showed AS and GL, respectively. In the logistic regression model, GL on the fusion image was a significant independent risk factor for predicting HE. However, when AS was used on conventional-like images, no factors significantly predicted HE. In the receiver operating characteristic curve analysis, the area under the curve of AS on the fusion images was 0.71, with a sensitivity and specificity of 66.7% and 76.2%, respectively. CONCLUSIONS: GL on fusion images of DECT in traumatic intracranial hemorrhage is a significant independent radiologic risk factor for predicting HE. The AS of DECT fusion images has improved sensitivity compared to that of conventional-like images.

Differentiation between hepatic angiomyolipoma and hepatocellular carcinoma in individuals who are not at-risk for hepatocellular carcinoma.

PURPOSE: To develop a practical methodfor differentiating hepatocellular carcinoma (HCC) from angiomyolipoma (AML) in individuals who are not at-risk for HCC. METHOD: We retrospectively enrolled consecutive patients who underwent gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) and pathological confirmation between January 2008 and April 2022. Patients who underwent prior treatment, those with multiple lesions, or those at-risk for HCC were excluded. The training cohort included patients with pathological confirmation between 2008 and 2019, whereas the validation cohort included the remaining cases. Independent reviews of the MRI were performed by two reviewers. Using the clinical and MRI findings, we developed AML-HCC score using Firth's logistic regression in the training cohort, and the diagnostic performance was validated in the validation cohort. RESULTS: Of the 206 patients, 156 were assigned to the training cohort (25 and 131 patients with AML and HCC, respectively) and 50 were assigned to the validation cohort (4 and 46 patients with AML and HCC, respectively). The AML-HCC score was defined as the sum of female (score 1), early draining vein (score 2), T2 homogeneity (score 1), necrosis or severe ischaemia (score -2), and HBP hyperintensity to spleen (score -1). When the AML-HCC score was ≥1, the sensitivity and specificity were 80% and 95% for the training cohort and 100% and 80% for the validation cohort, respectively. CONCLUSIONS: We developed and validated an AML-HCC score to differentiate between AML and HCC in individuals who are not at-risk for HCC, and our model demonstrated good diagnostic performance.

Pituitary Apoplexy After Leuprolide Therapy in a Breast Cancer Patient: A Case Report.

Pituitary apoplexy (PA) is a clinical syndrome resulting from sudden hemorrhage and/or infarction of the pituitary gland. Recent reports documented the development of PA secondary to treatment with gonadotropin-releasing hormone (GnRH) agonists for prostate cancer. A 52-year-old woman visited our emergency room with a severe headache, occurred 1 day prior. She underwent breast-conserving surgery for breast cancer 1 month prior. She was currently undergoing radiation and hormone therapy, consisting of leuprorelin. Brain contrast-enhanced MRI revealed a pituitary adenoma with internal hemorrhage in the sellar and suprasellar areas. Pachymeningeal enhancement was observed along the retroclival and bilateral frontal areas. The patient was diagnosed with PA and aseptic meningitis. The patient underwent total excision via transsphenoidal surgery 8 days after admission. The patient was pathologically diagnosed with a pituitary adenoma with necrosis. On immunochemical staining, the tumor was positive for follicle-stimulating hormone. The follow-up MRI revealed no evidence of residual tumor or an improved pachymeningeal enhancement. She is currently undergoing follow-up at the neurosurgery and endocrinology outpatient departments with no noted complications. In breast cancer patients receiving GnRH agonist therapy, PA may be rare complication.

Occurrence of Metachronous Intracranial Dural Arteriovenous Fistula after Embolization of Intracranial Dural Arteriovenous Fistula: A Case Report.

Intracranial dural arteriovenous fistula (DAVF) is an abnormal arteriovenous shunt accounting for approximately 10%-15% of all intracranial vascular malformations. Most intracranial DAVFs are solitary, but multiple lesions at different sites can rarely occur. Most intracranial multiple DAVFs are synchronous types, whereas metachronous lesions are relatively uncommon. Herein, we report a rare case of metachronous DAVF occurring after the embolization of a preceding lesion in a 75-year-old female.

IL-1ß promotes IL-9-producing Th cell differentiation in IL-2-limiting conditions through the inhibition of BCL6.

IL-9-producing CD4+ T helper cells, termed Th9 cells, differentiate from naïve precursor cells in response to a combination of cytokine and cell surface receptor signals that are elevated in inflamed tissues. After differentiation, Th9 cells accumulate in these tissues where they exacerbate allergic and intestinal disease or enhance anti-parasite and anti-tumor immunity. Previous work indicates that the differentiation of Th9 cells requires the inflammatory cytokines IL-4 and TGF-ß and is also dependent of the T cell growth factor IL-2. While the roles of IL-4 and TGF-ß-mediated signaling are relatively well understood, how IL-2 signaling contributes to Th9 cell differentiation outside of directly inducing the Il9 locus remains less clear. We show here that murine Th9 cells that differentiate in IL-2-limiting conditions exhibit reduced IL-9 production, diminished NF-kB activation and a reduced NF-kB-associated transcriptional signature, suggesting that IL-2 signaling is required for optimal NF-kB activation in Th9 cells. Interestingly, both IL-9 production and the NF-kB transcriptional signature could be rescued by addition of the NF-kB-activating cytokine IL-1ß to IL-2-limiting cultures. IL-1ß was unique among NF-kB-activating factors in its ability to rescue Th9 differentiation as IL-2 deprived Th9 cells selectively induced IL-1R expression and IL-1ß/IL-1R1 signaling enhanced the sensitivity of Th9 cells to limiting amounts of IL-2 by suppressing expression of the Th9 inhibitory factor BCL6. These data shed new light on the intertwined nature of IL-2 and NF-kB signaling pathways in differentiating Th cells and elucidate the potential mechanisms that promote Th9 inflammatory function in IL-2-limiting conditions.

Resolved Cerebral Venous Hypertension after Angioplasty of Central Venous Stenosis in a Hemodialysis Patient: A Case Report.

Stenosis of the central veins is a common complication in hemodialysis patients. However, cerebral venous hypertension and neurological symptoms caused by central vein stenosis are relatively rare. We present a rare case of cerebral venous hypertension in a 63-year-old male who showed venous reflux into the dural sinuses due to central venous stenosis on time-of-flight MR angiography. After management for central venous stenosis, the venous reflux disappeared.

Bile Acid Regulates Mononuclear Phagocytes and T Helper 17 Cells to Control Candida albicans in the Intestine.

Invasive Candida albicans (CA) infections often arise from the intestine and cause life-threatening infections in immunocompromised individuals. The role of gut commensal microbiota, metabolites, and host factors in the regulation of CA colonization in the intestine is poorly understood. Previous findings from our lab indicate that taurocholic acid (TCA), a major bile acid present in the intestine, promotes CA colonization and dissemination. Here, we report that oral administration of TCA to CA-infected mice significantly decreased the number of mononuclear phagocytes and CD4+ IL17A+ T helper 17 cells that play a critical role in controlling CA in the intestine. Collectively, our results indicate that TCA modulates mucosal innate and adaptive immune responses to promote CA colonization in the intestine.

Granzyme-Producing CD4 T Cells in Cancer and Autoimmune Disease.

CD4 T cells play important roles in promoting protective immunity and autoimmune disease. A great deal of attention has been given to the differentiation and function of subsets of cytokine-producing CD4 T cells (i.e., Th1, Th2, and Th17 cells) in these settings. However, others have also observed the accumulation of granzyme-producing CD4 T cells in tumors and in autoimmune patients that are distinct from their cytokine-producing counterparts. Despite the relatively large numbers of granzyme-producing cells in diseased tissues, their roles in driving disease have remained enigmatic. This review will focus on the phenotype(s) and roles of granzyme-producing CD4 T cells in cancer and autoimmunity. We will also examine how granzyme-producing cells interact with current therapeutics and speculate how they may be targeted during disease.

Granzyme A-producing T helper cells are critical for acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) can occur after hematopoietic cell transplant in patients undergoing treatment for hematological malignancies or inborn errors. Although CD4+ T helper (Th) cells play a major role in aGVHD, the mechanisms by which they contribute, particularly within the intestines, have remained elusive. We have identified a potentially novel subset of Th cells that accumulated in the intestines and produced the serine protease granzyme A (GrA). GrA+ Th cells were distinct from other Th lineages and exhibited a noncytolytic phenotype. In vitro, GrA+ Th cells differentiated in the presence of IL-4, IL-6, and IL-21 and were transcriptionally unique from cells cultured with either IL-4 or the IL-6/IL-21 combination alone. In vivo, both STAT3 and STAT6 were required for GrA+ Th cell differentiation and played roles in maintenance of the lineage identity. Importantly, GrA+ Th cells promoted aGVHD-associated morbidity and mortality and contributed to crypt destruction within intestines but were not required for the beneficial graft-versus-leukemia effect. Our data indicate that GrA+ Th cells represent a distinct Th subset and are critical mediators of aGVHD.

A case report of adult-onset Alexander disease clinically presenting as Parkinson's disease: is the comorbidity associated with genetic susceptibility?

BACKGROUND: Alexander disease is a rare neurological disease characterized by progressive spastic quadriparesis and bulbar palsy. Moreover, certain patients with adult-onset Alexander disease were often misdiagnosed as other neurodegenerative disorders. CASE PRESENTATION: Herein, we report an adult a 58-year-old woman presented with typical parkinsonism with good levodopa-responsiveness. The patient's dopamine transporter scanning showed significant striatal depletion, while her brain magnetic resonance imaging revealed bilateral tadpole shape of medulla oblongata and bilateral high signal intensity at both cerebellar dentate nuclei in T2-weighted images, suggesting the possibility of a genetic disorder beyond Parkinson's disease. The patient's genetic test resulted in known pathogenic glial fibrillary acidic protein variant, indicating Alexander disease. CONCLUSION: This unique case highlights genetically diagnosed Alexander disease may present with clinical Parkinson's disease.

Borden Type I Sigmoid Sinus Dural Arteriovenous Fistula Presenting as Subarachnoid Hemorrhage from a Feeding Artery Aneurysm of the Anterior Inferior Cerebellar Artery: A Case Report.

Dural arteriovenous fistula is an acquired vascular anomaly that can cause various symptoms. Here, we report a rare case of Borden type I sigmoid sinus dural arteriovenous fistula presenting as subarachnoid hemorrhage. Bleeding occurred from a side-wall aneurysm in the lateral pontomedullary segment of the anterior inferior cerebellar artery, which was a minor pial feeder. Features on imaging modalities, including brain CT, CT angiography, MR imaging/angiography and digital subtraction angiography, are described with a literature review.

[Evaluation of Cerebral Blood Flow Using Arterial Spin Labeling in Patients with Chronic Kidney Disease]. / 만성 콩팥병 환자들에서 동맥 스핀 표지 기법을 이용한 뇌 관류상태의 평가.

Purpose: This study aimed to compare the brain perfusion status of patients with chronic kidney disease to a normal control group to identify any significant differences. Materials and Methods: The perfusion state of the brain was measured by MRI using the arterial spin labeling technique in 36 patients undergoing hemodialysis due to chronic kidney disease and 36 normal controls. Images were then analyzed in a voxel-wise manner to detect brain areas showing significant perfusion differences between the two groups. Results: Patients with chronic kidney disease showed increased perfusion in the form of large clusters across the right fronto-parieto-temporal lobe and the left parieto-occipital lobe. In addition, perfusion increased in the bilateral thalami, midbrain, pons, and cerebellum (p < 0.01, family-wise error corrected). Conclusion: Brain perfusion appears to increase in patients with chronic kidney disease compared to normal controls. Uremic toxicity is thought to be the cause of this increase as it can cause damage to the microscopic blood vessels and their surrounding structures.

Application of Sequential Palladium Catalysis for the Discovery of Janus Kinase Inhibitors in the Benzo[ c]pyrrolo[2,3- h][1,6]naphthyridin-5-one (BPN) Series.

The present account describes the discovery and development of a new benzo[ c]pyrrolo[2,3- h][1,6]naphthyridin-5-one (BPN) JAK inhibitory chemotype that has produced selective JAK inhibitors. Sequential palladium chemistry was optimized for the rapid access to a focused library of derivatives to explore the structure-activity relationships of the new scaffold. Several compounds from the series displayed potencies in the low nanomolar range against the four members of the JAK family with various selectivity profiles. Compound 20a, with an azetidine amide side chain, showed the best selectivity for JAK1 kinase vs JAK2, JAK3, and TYK2, with low nanomolar potency (IC50 = 3.4 nM). On the other hand, BPNs 17b and 18 had good general activity against the JAK family with excellent kinome selectivity profiles. Many of the new BPNs inhibited JAK3-mediated STAT-5 phosphorylation, the production of inflammatory cytokines, and the proliferation of primary T cells. Moreover, BPN 17b showed very similar in vivo results to tofacitinib in a rheumatoid arthritis animal model.

RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells.

Langerhans cells (LC) are the prototype langerin-expressing dendritic cells (DC) that reside specifically in the epidermis, but langerin-expressing conventional DCs also reside in the dermis and other tissues, yet the factors that regulate their development are unclear. Because retinoic acid receptor alpha (RARα) is highly expressed by LCs, we investigate the functions of RARα and retinoic acid (RA) in regulating the langerin-expressing DCs. Here we show that the development of LCs from embryonic and bone marrow-derived progenitors and langerin+ conventional DCs is profoundly regulated by the RARα-RA axis. During LC differentiation, RARα is required for the expression of a LC-promoting transcription factor Runx3, but suppresses that of LC-inhibiting C/EBPß. RARα promotes the development of LCs and langerin+ conventional DCs only in hypo-RA conditions, a function effectively suppressed at systemic RA levels. Our findings identify positive and negative regulatory mechanisms to tightly regulate the development of the specialized DC populations.

Effector T Helper Cell Subsets in Inflammatory Bowel Diseases.

The gastrointestinal tract is a site of high immune challenge, as it must maintain a delicate balance between tolerating luminal contents and generating an immune response toward pathogens. CD4+ T cells are key in mediating the host protective and homeostatic responses. Yet, CD4+ T cells are also known to be the main drivers of inflammatory bowel disease (IBD) when this balance is perturbed. Many subsets of CD4+ T cells have been identified as players in perpetuating chronic intestinal inflammation. Over the last few decades, understanding of how each subset of Th cells plays a role has dramatically increased. Simultaneously, this has allowed development of therapeutic innovation targeting specific molecules rather than broad immunosuppressive agents. Here, we review the emerging evidence of how each subset functions in promoting and sustaining the chronic inflammation that characterizes IBD.

Multi c-BN Coatings by r.f Diode Sputtering and Investigation of Wear Behavior.

Cubic boron nitride (c-BN) films on tool substrates are tendency to delaminate. Therefore, many research groups have studied improvement of c-BN synthesis method and deposition processes due to many potential applications. In this paper, we show that the adhesion property of c-BN layer system can be improved by deposing multi c-BN layers. The multi c-BN layers were deposited by r.f (13.56 MHz) diode sputtering apparatus on cemented carbide tool substrates with a TiAlN adhesion layer. For industrial applications, we performed turning and milling experiments under dry and high speed cutting conditions. In this multi c-BN layer system, the lifetime of the tool is affected by the physical properties of the substrate and coated layers such as substrate grain size, thickness of the TiAlN and first c-BN layer and the total number of c-BN layers in this system. Mostly, fine grain size substrates showed longer lifetimes of over 4 times than raw one. In the turning performance, mono TiAlN layer systems were about two times lower lifetime than mono and multi c-BN layer system, moreover, we could be improved adhesion property for milling performance on tool substrates with binary multi c-BN layer systems under dry and high speed cutting conditions. The new application results of the multi c-BN layer system confirm that the high potential of c-BN coatings on cutting tools.

Recently Uncontrolled Glycemia in Diabetic Patients Is Associated with the Severity of Intracranial Atherosclerosis.

BACKGROUND AND PURPOSE: Diabetes mellitus is a specific risk factor for intracranial atherosclerosis (ICAS) regardless of race. However, it is largely unknown whether poor glycemic control is associated with the severity of ICAS in diabetic patients. METHODS: We selected diabetic patients with acute ischemic stroke who were prospectively registered between March 2005 and December 2015. The patients who had a high-risk source of cardiogenic embolism were excluded. ICAS was graded from 0 to 3 by the number of significant (≥50%) stenoses on intracranial magnetic resonance angiography, and was divided into 4 types: unilateral anterior, bilateral anterior, posterior, and anterior plus posterior. Ordinal and multinomial regression tests were applied for the factors influencing the number and types of ICAS. RESULTS: A total of 774 patients with noncardioembolic acute ischemic stroke with diabetes were enrolled. The multiplicity of ICAS was independently associated with age (odds ratio [OR], 1.035 per 1 year, 1.018-1.052; P < .001), hypertension (OR, 1.992, 1.336-2.965; P = .001), and glycated hemoglobin (HbA1c; OR, 1.207 per 1%, 1.089-1.338; P < .001) in the ordinal regression model. In multinomial regression, bilateral anterior stenosis tended to be correlated with age (OR, 1.042, 1.008-1.077; P = .016) and HbA1c (OR, 1.201 per 1%, .991-1.520; P = .057). Both anterior and posterior stenoses were significantly associated with age (OR, 1.056, 1.029-1.084; P < .001), hypertension (OR, 2.584, 1.404-4.762; P = .002), and HbA1c (OR, 1.272, 1.070-1.511; P = .006). CONCLUSIONS: Age, concomitant hypertension, and HbA1c were factors associated with multiple intracranial stenoses. Further study is warranted to elucidate whether poor glycemic control facilitates ICAS in diabetic patients.

Evaluation for fracture patterns around the wrist on three-dimensional extremity computed tomography, especially focused on the triquetrum.

INTRODUCTION: To describe fracture patterns of triquetrum and analyse them according to fracture classifications, anatomy of intrinsic carpal ligaments and comparison with other wrist fractures. METHODS: We retrospectively reviewed 297 three-dimensional extremity computed tomographies (CTs) on wrist fractures from October 2007 to January 2012. We initially classified the fractures according to the involved bones and analyzed them according to the patterns of triquetrum fractures, associated carpal bone fractures and presence of combined distal radius fractures. We also correlated the fracture patterns with the patient's injury patterns. RESULTS: A total of 297 CTs and 291 patients were included (162 males and 129 females; mean age, 47.8 years). There were a total of 131 carpal bone fractures in 102 patients of 102 CTs. Triquetrum fractures were the most commonly observed cases (36 cases/27.5%). For the triquetrum fractures, the following types were observed: 26 dorsal, five volar, two comminuted fractures are observed in triquetrum. Three other triquetrum fractures show combined forms of other carpal bone fractures. For the combined distal radius fractures, 10 dorsal and two volar fractures were shown. Out of 187 distal radius fractures, 20 showed carpal bone fractures (10.7%). There were no differences in injury patterns according to the fracture patterns. The most common pattern of injury was falling on the outstretched hand, followed by fall from height. CONCLUSION: The dorsum of triquetrum is more frequently fractured than the volar aspect. The number of carpal bone fractures among the patients who have distal radius fractures is higher than usual expectation.

Computational Fluid Dynamics of Intracranial and Extracranal Arteries using 3-Dimensional Angiography: Technical Considerations with Physician's Point of View.

We investigate the potentials and limitations of computational fluid dynamics (CFD) analysis of patient specific models from 3D angiographies. There are many technical problems in acquisition of proper vascular models, in pre-processing for making 2D surface and 3D volume meshes and also in post-processing steps for display the CFD analysis. We hope that our study could serves as a technical reference to validating other tools and CFD results.