Conversion map from quantitative parameter mapping to myelin water fraction: comparison with R1·R2* and myelin water fraction in white matter.

OBJECTIVE: To clarify the relationship between myelin water fraction (MWF) and R1⋅R2* and to develop a method to calculate MWF directly from parameters derived from QPM, i.e., MWF converted from QPM (MWFQPM). MATERIALS AND METHODS: Subjects were 12 healthy volunteers. On a 3 T MR scanner, dataset was acquired using spoiled gradient-echo sequence for QPM. MWF and R1⋅R2* maps were derived from the multi-gradient-echo (mGRE) dataset. Volume-of-interest (VOI) analysis using the JHU-white matter (WM) atlas was performed. All the data in the 48 WM regions measured VOI were plotted, and quadratic polynomial approximations of each region were derived from the relationship between R1·R2* and the two-pool model-MWF. The R1·R2* map was converted to MWFQPM map. MWF atlas template was generated using converted to MWF from R1·R2* per WM region. RESULTS: The mean MWF and R1·R2* values for the 48 WM regions were 11.96 ± 6.63%, and 19.94 ± 4.59 s-2, respectively. A non-linear relationship in 48 regions of the WM between MWF and R1·R2* values was observed by quadratic polynomial approximation (R2 ≥ 0.963, P < 0.0001). DISCUSSION: MWFQPM map improved image quality compared to the mGRE-MWF map. Myelin water atlas template derived from MWFQPM may be generated with combined multiple WM regions.

Comparison of Non-ephedrine Constituents from Ephedra Plants Cultivated in Japan.

Ephedra plants, the main components of which are ephedrine alkaloids, are used as traditional medicines in Eastern Asian countries. In this study, we isolated non-ephedrine constituents from various Ephedra plant species cultivated in Japan. HPLC analysis suggested that kynurenic acid and its derivatives accumulated in a wide range of Ephedra plant species. Furthermore, a large amount of (2R,3S)-O-benzoyl isocitrate has been isolated from E. intermedia. This study suggests that Ephedra plants have diverse non-ephedrine constituents.

A blurring correction method suitable to analyze quantitative x-ray images derived from energy-resolving photon counting detector.

Objective.The purpose of this study is to propose a novel blurring correction method that enables accurate quantitative analysis of the object edge when using energy-resolving photon counting detectors (ERPCDs). Although the ERPCDs have the ability to generate various quantitative analysis techniques, such as the derivations of effective atomic number (Zeff) and bone mineral density values, at the object edge in these quantitative images, accurate quantitative information cannot be obtained. This is because image blurring prevents the gathering of accurate primary x-ray attenuation information.Approach.We developed the following procedure for blurring correction. A 5 × 5 pixels masking region was set as the processing area, and the pixels affected by blurring were extracted from the analysis of pixel value distribution. The blurred pixel values were then corrected to the proper values estimated by analyzing minimum and/or maximum values in the set mask area. The suitability of our correction method was verified by a simulation study and an experiment using a prototype ERPCD.Main results. WhenZeffimage of aluminum objects (Zeff= 13) were analyzed without applying our correction method, regardless of raw data or correction data applying a conventional edge enhancement method, the properZeffvalues could not be derived for the object edge. In contrast, when applying our correction method, 82% of pixels affected by blurring were corrected and the properZeffvalues were calculated for those pixels. As a result of investigating the applicability limits of our method through simulation, it was proven that it works effectively for objects with 4 × 4 pixels or more.Significance. Our method is effective in correcting image blurring when the quantitative image is calculated based on multiple images. It will become an in-demand technology for putting a quantitative diagnosis into actual medical examinations.

Metagenomic gut microbiome analysis of Japanese patients with multiple chemical sensitivity/idiopathic environmental intolerance.

BACKGROUND: Although the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying central nervous system diseases. However, the relationship　between the gut microbiota and MCS remains unclear. This study aimed to identify gut microbiota variations associated with MCS using shotgun metagenomic sequencing of fecal samples. METHODS: We prospectively recruited 30 consecutive Japanese female patients with MCS and analyzed their gut microbiomes using shotgun metagenomic sequencing. The data were compared with metagenomic data obtained from 24 age- and sex-matched Japanese healthy controls (HC). RESULTS: We observed no significant difference in alpha and beta diversity of the gut microbiota between the MCS patients and HC. Focusing on the important changes in the literatures, at the genus level, Streptococcus, Veillonella, and Akkermansia were significantly more abundant in MCS patients than in HC (p < 0.01, p < 0.01, p = 0.01, respectively, fold change = 4.03, 1.53, 2.86, respectively). At the species level, Akkermansia muciniphila was significantly more abundant (p = 0.02, fold change = 3.3) and Faecalibacterium prausnitzii significantly less abundant in MCS patients than in HC (p = 0.03, fold change = 0.53). Functional analysis revealed that xylene and dioxin degradation pathways were significantly enriched (p < 0.01, p = 0.01, respectively, fold change = 1.54, 1.46, respectively), whereas pathways involved in amino acid metabolism and synthesis were significantly depleted in MCS (p < 0.01, fold change = 0.96). Pathways related to antimicrobial resistance, including the two-component system and cationic antimicrobial peptide resistance, were also significantly enriched in MCS (p < 0.01, p < 0.01, respectively, fold change = 1.1, 1.2, respectively). CONCLUSIONS: The gut microbiota of patients with MCS shows dysbiosis and alterations in bacterial functions related to exogenous chemicals and amino acid metabolism and synthesis. These findings may contribute to the further development of treatment for MCS. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Clinical Trials Registry as UMIN000031031. The date of first trial registration: 28/01/2018.

Differences of white matter structure for diffusion kurtosis imaging using voxel-based morphometry and connectivity analysis.

Objectives: In a clinical study, diffusion kurtosis imaging (DKI) has been used to visualize and distinguish white matter (WM) structures' details. The purpose of our study is to evaluate and compare the diffusion tensor imaging (DTI) and DKI parameter values to obtain WM structure differences of healthy subjects. Methods: Thirteen healthy volunteers (mean age, 25.2 years) were examined in this study. On a 3-T MRI system, diffusion dataset for DKI was acquired using an echo-planner imaging sequence, and T1-weghted (T1w) images were acquired. Imaging analysis was performed using Functional MRI of the brain Software Library (FSL). First, registration analysis was performed using the T1w of each subject to MNI152. Second, DTI (eg, fractional anisotropy [FA] and each diffusivity) and DKI (eg, mean kurtosis [MK], radial kurtosis [RK], and axial kurtosis [AK]) datasets were applied to above computed spline coefficients and affine matrices. Each DTI and DKI parameter value for WM areas was compared. Finally, tract-based spatial statistics (TBSS) analysis was performed using each parameter. Results: The relationship between FA and kurtosis parameters (MK, RK, and AK) for WM areas had a strong positive correlation (FA-MK, R2 = 0.93; FA-RK, R2 = 0.89) and a strong negative correlation (FA-AK, R2 = 0.92). When comparing a TBSS connection, we found that this could be observed more clearly in MK than in RK and FA. Conclusions: WM analysis with DKI enable us to obtain more detailed information for connectivity between nerve structures. Advances in knowledge: Quantitative indices of neurological diseases were determined using segmenting WM regions using voxel-based morphometry processing of DKI images.

Determination of Alzheimer's disease based on morphology and atrophy using machine learning combined with automated segmentation.

BACKGROUND: To evaluate the degree of cerebral atrophy for Alzheimer's disease (AD), voxel-based morphometry has been performed with magnetic resonance imaging. Detailed morphological changes in a specific tissue area having the most evidence of atrophy were not considered by the machine-learning technique. PURPOSE: To develop a machine-learning system that can capture morphology features for determination of atrophy of brain tissue in early-stage AD and classification of healthy participants or patients. MATERIAL AND METHODS: Three-dimensional T1-weighted (3D-T1W) data were obtained from AD Neuroimaging Initiative (200 healthy controls and 200 patients with early-stage AD). Automated segmentation of 3D-T1W data was performed. Deep learning (DL) and support vector machine (SVM) were trained using 66-segmented volume values as input and AD diagnosis as output. DL was performed using 66 volume values or gray matter (GM) and white matter (WM) volume values. SVM learning was performed using 66 volume values and six regions with high variable importance. 3D convolutional neural network (3D-CNN) was trained using the segmented images. Accuracy and area under curve (AUC) were obtained. Variable importance was evaluated from logistic regression analysis. RESULTS: DL for GM and WM volume values, accuracy 0.6; SVM for all volume values, accuracy 0.82 and AUC 0.81; DL for all volume values, accuracy 0.82 and AUC 0.8; 3D-CNN using segmental images of the whole brain, accuracy 0.5 and AUC 0.51. SVM using volume values of six regions, accuracy 0.82; image-based 3D-CNN, highest accuracy 0.69. CONCLUSION: Our results show that atrophic features are more considerable than morphological features in the early detection of AD.

Simplified assessment for chemical exchanged saturation transfer (CEST) imaging: local offset frequency and CEST effect.

The aim of this study is to develop a novel phantom for the evaluation of clinical CEST imaging settings, e.g., B0 and B1 field inhomogeneities, CEST contrast, and post-processing. We made a phantom composed of two slice sections: a grid section for local offset frequency evaluation and a sample section for CEST effect evaluation using different concentrations of an egg white albumin solution. On a 3 Tesla MR scanner, a phantom study was performed using CEST imaging; the mean B1 amplitudes were set at 1.2 and 1.9 µT, and CEST images with and without B0 corrections were acquired. Next, region of interest (ROI) analysis was performed for each slice. Then, CEST images with and without B0 corrections were compared at each B1 amplitude. The B0 corrected Z-spectrums at each local region in the grid section showed a shifting of the curve bottom to 0 ppm. Z-spectrum at B1 = 1.9 µT showed a broader curve shape than that at 1.2 µT. Moreover, MTRasym values at 3.5 ppm for each albumin sample at B1 = 1.9 µT were about two times higher than those at 1.2 µT. Our phantom enabled us to evaluate and optimize B0 inhomogeneity and the CEST effect at the B1 amplitude.

Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

PURPOSE: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay. EXPERIMENTAL DESIGN: FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. RESULTS: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL. CONCLUSIONS: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

Performance of elastic x-ray shield made by embedding Bi2 O3 particles in porous polyurethane.

BACKGROUND: Many healthcare institutions have guidelines concerning the usage of protective procedures, and various x-ray shields have been used to reduce unwanted radiation exposure to medical staff and patients when using x-rays. Most x-ray shields are in the form of sheets and lack elasticity, which limits their effectiveness in shielding areas with movement, such as the thyroid. To overcome this limitation, we have developed an innovative elastic x-ray shield. PURPOSE: The purpose of this study is to explain the methodology for developing and evaluating a novel elastic x-ray shield with sufficient x-ray shielding ability. Furthermore, valuable knowledge and evaluation indices are derived to assess our shield's performance. METHODS: Our x-ray shield was developed through a process of embedding Bi2 O3 particles into porous polyurethane. Porous polyurethane with a thickness of 10 mm was dipped into a solution of water, metal particles, and chemical agents. Then, it was air-dried to fix the metal particles in the porous polyurethane. Thirteen investigational x-ray shields were fabricated, in which Bi2 O3 particles at various mass thicknesses (ranging from 585 to 2493 g/m2 ) were embedded. To determine the performance of the shielding material, three criteria were evaluated: (1) Dose Reduction Factor ( D R F $DRF$ ), measured using inverse broad beam geometry; (2) uniformity, evaluated from the standard deviation ( S D $SD$ ) of the x-ray image obtained using a clinical x-ray imaging detector; and (3) elasticity, evaluated by a compression test. RESULTS: The elastic shield with small pores, containing 1200 g/m2 of the metal element (Bi), exhibited a well-balanced performance. The D R F $DRF$ was approximately 80% for 70 kV diagnostic x-rays. This shield's elasticity was -0.62 N/mm, a loss of only 30% when compared to porous polyurethane without metal. Although the non-uniformity of the x-ray shield leads to poor shielding ability, it was found that the decrease in the shielding ability can be limited to a maximum of 6% when the shield is manufactured so that the S D $SD$ of the x-ray image of the shield is less than 10%. CONCLUSIONS: It was verified that an elastic x-ray shield that offers an appropriate reduction in radiation exposure can be produced by embedding Bi2 O3 particles into porous polyurethane. Our findings can lead to the development of novel x-ray shielding products that can reduce the physical and mental stress on users.

Radiation exposure doses to the surgical team during hip surgery is significantly higher during lateral imaging than posteroanterior imaging: a cadaveric simulation study.

BACKGROUND: Fluoroscopy is indispensable when determining appropriate and effective interventions in orthopedic surgery. On the other hand, there is growing concern about the health hazards of occupational radiation exposure. The aim of this cadaveric simulation study was to measure radiation exposure doses to the surgical team during hip surgery. METHODS: We reproduced the intraoperative setting of hip surgery using 7 fresh frozen cadavers (5 male, 2 female) to simulate patients and mannequins to simulate the surgeon, scrub nurse, and anesthesiologist. Six real-time dosimeters were mounted at sites corresponding to the optic lens, thyroid gland, chest, gonads, foot, and hand on each mannequin. The radiation exposure dose to each team member was measured during posteroanterior and lateral fluoroscopic imaging. RESULTS: Radiation exposure doses to the surgeon were significantly higher during 3 min of lateral imaging than during 3 min of posteroanterior imaging at the optic lens (8.1 times higher), thyroid gland (10.3 times), chest (10.8 times), and hand (19.8 times) (p = 0.018, p = 0.018, p = 0.018, and p = 0.018, respectively). During lateral imaging, the radiation doses to the nurse were 0.16, 0.12, 0.09, 0.72, and 0.38 times those to the surgeon at the optic lens, thyroid, chest, gonads, and foot, respectively. The radiation dose to the anesthesiologist was zero at all anatomic sites during posteroanterior imaging and very small during lateral imaging. CONCLUSIONS: Radiation exposure dose was significantly higher during lateral imaging up to 19.8 times comparing to the posteroanterior imaging. It is effective to reduce the lateral imaging time for reducing the intraoperative radiation exposure. In addition, appropriate distance from fluoroscopy resulted in very low exposure for nurses and anesthesiologists. Surgeon should pay attention that surgical staff do not get closer than necessary to the irradiation field.

Genetic alterations that deregulate RB and PDGFRA signaling pathways drive tumor progression in IDH2-mutant astrocytoma.

In IDH-mutant astrocytoma, IDH2 mutation is quite rare and biological mechanisms underlying tumor progression in IDH2-mutant astrocytoma remain elusive. Here, we report a unique case of IDH2 mutant astrocytoma, CNS WHO grade 3 that developed tumor progression. We performed a comprehensive genomic and epigenomic analysis for primary and recurrent tumors and found that both tumors harbored recurrent IDH2R172K and TP53R248W mutation with CDKN2A/B hemizygous deletion. We also found amplifications of CDK4 and MDM2 with PDGFRA gain in the recurrent tumor and upregulated protein expressions of these genes. We further developed, for the first time, a xenograft mouse model of IDH2R172K and TP53R248W mutant astrocytoma from the recurrent tumor, but not from the primary tumor. Consistent with parent recurrent tumor cells, amplifications of CDK4 and MDM2 and PDGFRA gain were found, while CDKN2A/B was identified as homozygous deletion in the xenografts, qualifying for integrated diagnosis of astrocytoma, IDH2-mutant, CNS WHO grade 4. Cell viability assay found that CDK4/6 inhibitor and PDGFR inhibitor potently decreased cell viability in recurrent tumor cells, as compared to primary tumor cells. These findings suggest that gene alterations that activate retinoblastoma (RB) signaling pathways and PDGFR may drive tumor progression and xenograft formation in IDH2-mutant astrocytoma, which is equivalent to progressive IDH1-mutant astrocytoma. Also, our findings suggest that these genomic alterations may represent therapeutic targets in IDH2-mutant astrocytoma.

Glucagon-like Peptide-1 Receptor Pathway Attenuates Platelet Activation in Aspirin-Exacerbated Respiratory Disease.

Platelets are key contributors to allergic asthma and aspirin-exacerbated respiratory disease (AERD), an asthma phenotype involving platelet activation and IL-33-dependent mast cell activation. Human platelets express the glucagon-like peptide-1 receptor (GLP-1R). GLP-1R agonists decrease lung IL-33 release and airway hyperresponsiveness in mouse asthma models. We hypothesized that GLP-1R agonists reduce platelet activation and downstream platelet-mediated airway inflammation in AERD. GLP-1R expression on murine platelets was assessed using flow cytometry. We tested the effect of the GLP-1R agonist liraglutide on lysine-aspirin (Lys-ASA)-induced changes in airway resistance, and platelet-derived mediator release in a murine AERD model. We conducted a prospective cohort study comparing the effect of pretreatment with liraglutide or vehicle on thromboxane receptor agonist-induced in vitro activation of platelets from patients with AERD and nonasthmatic controls. GLP-1R expression was higher on murine platelets than on leukocytes. A single dose of liraglutide inhibited Lys-ASA-induced increases in airway resistance and decreased markers of platelet activation and recruitment to the lung in AERD-like mice. Liraglutide attenuated thromboxane receptor agonist-induced activation as measured by CXCL7 release in plasma from patients with AERD and CD62P expression in platelets from both patients with AERD (n = 31) and nonasthmatic, healthy controls (n = 11). Liraglutide, a Food and Drug Administration-approved GLP-1R agonist for treatment of type 2 diabetes and obesity, attenuates in vivo platelet activation in an AERD murine model and in vitro activation in human platelets in patients with and without AERD. These data advance the GLP-1R axis as a new target for platelet-mediated inflammation warranting further study in asthma.

[Circumscribed Astrocytic Gliomas].

In the fifth edition central nervous system tumours volume of the WHO Classification of Tumours series, gliomas, glioneuronal tumors, and neuronal tumors are divided into six groups. The term "circumscribed" is used to refer to a relatively contained growth pattern, as compared to other inherently "diffuse" tumors. Circumscribed astrocytic gliomas include six types: pilocytic astrocytoma, high-grade astrocytoma with piloid features, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, and astroblastoma, MN1-altered. The vast majority of circumscribed astrocytic gliomas harbor genetic alterations in the mitogen-activated protein kinase pathway. Here, we review the circumscribed astrocytic gliomas, including etiology, clinical and imaging features, pathology and molecular genetics, treatment, and prognosis. This study will lead to better understanding of these newly classified tumors.

A Cadaveric Simulation Study of Radiation Exposure to the Surgical Team during Fluoroscopic Spinal Surgery: How Much Are We Exposed?

Introduction: The harmful effects of long-term low-dose radiation have been well known. There are few comprehensive reports evaluating concrete real exposure doses for each part of a surgeon, assistant surgeon, scrub nurse, and anesthesiologist associated with fluoroscopic spinal procedures. This research aimed to quantify the radiation exposure dose to surgical team members during C-arm fluoroscopy-guided spinal surgery. Methods: Seven fresh cadavers were irradiated for 1 and 3 min with C-arm fluoroscopy. The position of the X-ray source was under the table, over the table, and laterally. The radiation exposure doses were measured at the optic lens, thyroid gland, and hand in mannequins used to simulate surgical team members. Results: A significant difference was observed in the radiation exposure dose according to the position of the X-ray source and the irradiated body area. The risk of scatter radiation exposure was the biggest for the lateral position (nearly 30-fold that for the position under the table). All radiation exposure doses were positively correlated with irradiation time. Conclusions: The occupational radiation exposure dose to surgical team members during C-arm fluoroscopy-guided lumbar spinal procedures varies according to the X-ray source position. Our findings would help surgical team members to know the risk of radiation exposure during various fluoroscopic procedures. Surgeons in particular need to reduce their radiation exposure by using appropriate shielding and technique.

Omalizumab ameliorates extrarespiratory symptoms in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Omalizumab, an anti-IgE antibody, has clinical efficacy against respiratory symptoms of aspirin-exacerbated respiratory disease (AERD). However, some patients with AERD also present with extrarespiratory (chest, gastrointestinal, and/or cutaneous) symptoms, which are resistant to conventional treatment but can be alleviated by systemic corticosteroids. OBJECTIVE: We evaluated the efficacy of omalizumab on extrarespiratory symptoms related to AERD. METHODS: In study 1, a total of 27 consecutive patients with AERD initially prescribed omalizumab at Sagamihara National Hospital between July 2009 and March 2019 were retrospectively studied. Frequency of exacerbations of AERD-related extrarespiratory symptoms was compared before and after omalizumab treatment. In study 2, we reported 3 AERD cases with aspirin challenge-induced extrarespiratory symptoms among patients studied in our previous randomized trial (registration UMIN000018777), which evaluated the effects of omalizumab on hypersensitivity reactions during aspirin challenge to AERD patients. Extrarespiratory symptoms induced during the aspirin challenge were compared between placebo and omalizumab phases. RESULTS: In study 1, omalizumab treatment was associated with decrease in frequency of exacerbation of chest pain (no. [%] of patients with exacerbation frequency ≥1 time per year, 6 [22.2%] vs 0; P < .001), gastrointestinal symptoms (9 [33.3%] vs 2 [7.4%]; P = .016), and cutaneous symptoms (16 [59.3%] vs 2 [7.4%]; P < .001), even under conditions of treatment-related reduction in systemic corticosteroid dose. Omalizumab also attenuated all the extrarespiratory symptoms during aspirin challenge in study 2. CONCLUSION: Omalizumab ameliorated extrarespiratory symptoms at baseline (without aspirin exposure) and during aspirin challenge.

Evaluation of a Novel Combination Therapy, Based on Trifluridine/Tipiracil and Fruquintinib, against Colorectal Cancer.

INTRODUCTION: Trifluridine/tipiracil hydrochloride (FTD/TPI, Lonsurf®) is an oral antineoplastic agent that has been approved as late-stage chemotherapy for colorectal cancer. Its major mechanism of action is the dysfunction of tumoral DNA including DNA strand breaks and decreased replication. Fruquintinib (ELUNATE®) is a novel kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-1, -2, and -3. In this study, we evaluated the antitumor activity of combination therapy with FTD/TPI and fruquintinib in vivo. METHODS: The enhancement of the antitumor effects with FTD/TPI and fruquintinib combination, compared to the single drugs given alone was evaluated using two human colorectal cancer xenografts in nude mouse models. FTD/TPI (200 mg/kg) was orally administered for 5 consecutive days followed by 2 days of rest in a 7-day period. Fruquintinib (10 mg/kg) was orally administered consecutively for 2 and 3 weeks in SW48 and HCT 116 tumor-bearing models, respectively. After treatment with these agents, the microvessel density was evaluated by CD31 immunohistochemical analyses. RESULTS: In both models, FTD/TPI and fruquintinib significantly inhibited tumor growth, and the activity of the combined treatment was significantly superior to that of either monotherapy. Body weight loss of greater than 20% was not observed in any group. A histochemical analysis showed nuclei enlargement, abnormal mitosis, and karyorrhexis in the FTD/TPI treatment group. The microvessel density in the HCT 116 tumors treated with FTD/TPI and fruquintinib was significantly lower than that in the control group. CONCLUSION: The combination of FTD/TPI and fruquintinib could be a promising treatment option for colorectal cancer.

Myelin-weighted imaging derived from quantitative parameter mapping.

PURPOSE: We developed a novel method which is applicable to visualize contrast according to myelin components in the human brain using relaxation time derived from quantitative parameter mapping magnetic resonance imaging (QPM-MRI). MATERIALS AND METHODS: Using healthy volunteer data (n = 10), we verified that our method demonstrated that the myelin-weighted contrast increased proportionally by products R1 and R2*, i.e., QPM-myelin-weighted image, in which modified T1-weighted/T2-weighted (T1w/T2w) ratio mapping method was applied. We compared measurement values in white matter (WM) and gray matter (GM) regions of the T1w/T2w ratio and R1·R2* product maps of healthy volunteers. Linear regression analysis between each value. Mann Whitney U test between WM and GM signals in each myelin map. In addition, Additionally, QPM-myelin-weighted image was applied to a 32-year-old female MS patient. RESULTS: Linear regression analysis showed a highly significant correlation between conventional T1w/T2w ratios and R1·R2* products derived from QPM (R = 0.73, P < 0.0001). Moreover, there is a significant difference between WM and GM structures in each myelin images (both, P < 0.0001). Additionally, in a clinical case, MS lesions enabled observation of not only MS plaques but also heterogeneous myelin signal loss associated with demyelination more clearly than T2w image and conventional T1w/T2w ratio image. CONCLUSION: Our myelin-weighted imaging technique using QPM may be useful for myelin visualization and is expected to become independent of measurement conditions due to having quantitative characteristics of QPM itself.

Adrenal Insufficiency Secondary to Abrupt Dose Reduction of Topical Corticosteroid Therapy after Starting Brodalumab for Psoriasis: A Case Report.

The risk of treating psoriasis with biologic drugs in patients treated with topical corticosteroids over prolonged periods requires careful attention to their underlying adrenal insufficiency because the development of adrenal insufficiency symptoms frequently occurs after cessation of the topical corticosteroids: the dose and duration of topical corticosteroid therapy and etretinate use correlate with risk. In this case report, we present a 65-year-old man with psoriatic erythroderma who developed arthralgia, joint pain, muscle pain, fatigue, and headache after starting brodalumab and a reduction of topical potent corticosteroid doses in the treatment of psoriasis. Because his plasma cortisol levels were decreased and the levels and various signs recovered by administration of physiological doses of hydrocortisone replacement, we concluded that these clinical signs observed after starting brodalumab could be clinical manifestations of adrenal insufficiency secondary to an abrupt reduction in the amount of a topical corticosteroid, but not adverse effects of brodalumab. We found another 2 cases with psoriatic erythroderma who developed secondary to adrenal insufficiency after starting biologic drugs and a reduction of topical corticosteroid doses in the literature. Notably, the side effects of brodalumab include arthralgia, headache, and fatigue, and suspicion of side effects may include the clinical manifestations of adrenal insufficiency. Clinicians have to predict adrenal insufficiency secondary to an abrupt reduction of topical corticosteroids after remarkable improvement of psoriasis by biologics. The routine monitoring of plasma cortisol levels is necessary for all erythrodermic psoriasis patients treated with topical corticosteroids over prolonged periods before starting biologics.

Characterization of Triterpene Saponin Glycyrrhizin Transport by Glycyrrhiza glabra.

Glycyrrhizin (GL), a triterpene compound produced by Glycyrrhiza species, is a crucial pharmacologically active component of crude drugs. In contrast to the biosynthesis of GL in plants, little is known about GL transport and accumulation in plants. The transport mechanism of GL was characterized using cultured cells of Glycyrrhiza glabra. Cultured cells of G. glabra efficiently incorporated exogenously supplied GL. Proton pump inhibitors, such as probenecid and niflumic acid, as well as a protonophore (carbonylcyanide m-chlorophenylhydrazone), markedly inhibited GL uptake by cultured cells, whereas vanadate exhibited a moderate inhibition. Furthermore, GL transport by G. glabra tonoplast vesicles is dependent not on a H+-electrochemical gradient but MgATP and is markedly inhibited by vanadate. These results suggest that GL uptake by cultured cells is mediated by a H+-symporter in the plasma membrane and an ATP-binding cassette transporter, which has high specificity for the aglycone structure of GL on the tonoplast.