Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan

Comparison of the current study with other sorafenib-interferon combination studies and with single-agent sorafenib studies [25]. (XLSX 12 kb

Usefulness of fluorine-18 fluorodeoxyglucose-positron emission tomography in management strategy for thymic epithelial tumors

Background: This study investigated the usefulness of fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) during the treatment of thymic epithelial tumors in combination with Ki-67 evaluation based on surgical cases in our department. Methods: Between November 2003 and May 2011, 39 patients with thymic epithelial tumor underwent preoperative FDG-PET. The maximum standardized uptake value (SUVmax) of each category within Masaoka stage, World Health Organization classification, tumor diameter, myasthenia gravis, and Ki-67 label index were compared. To examine risk factors for relapse, SUVmax, age, sex, and surgical radicality were investigated in addition to those items. Results: The mean SUVmax was 4.5 (range, 1.2 to 14.6) and was significantly higher for Masaoka stage IV than for I and II (all p < 0.008) and for World Health Organization classified thymic cancer compared with all other types (all p < 0.0001). Mean SUVmax revealed significantly higher values for large tumors than for small tumors (p = 0.02). Mean SUVmax was significantly higher for high Ki-67-positive samples (p = 0.0004), indicating a strong correlation between SUVmax and the Ki-67 label index (ρ = 0.77, p = 0.0001). SUVmax accurately reflected therapeutic efficacy in patients with induction therapy. Univariate analysis revealed Masaoka stages III and IV and pathologically incomplete resection as risk factors for relapse. On multivariate analysis, independent risk factors for relapse comprised only Masaoka stages III and IV. Conclusions: FDG-PET SUVmax does reflect proliferation and invasiveness of thymic epithelial tumors and can provide an index for diagnosis and treatment, although it is not a risk factor for relapse. FDG-PET is also useful for evaluating induction therapy efficacy and detecting relapse. © 2013 The Society of Thoracic Surgeons

Arterial spin labeling image findings in the acute phase in paediatric patients with acute encephalopathy with biphasic seizures and late reduced diffusion

IntroductionDiagnosing acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) after the first seizure (early seizure/seizures, ES/ESs) is challenging because a reduced apparent diffusion coefficient (ADC) in the cortical or subcortical white matter, often described as having a “bright-tree appearance (BTA),” is usually not observed until secondary seizures (late seizures, LSs) occur. Previous studies have reported hypoperfusion on arterial spin labeling (ASL) within 24 h after ES/ESs in patients with AESD and hyperperfusion within 24 h after LS onset. This study aimed to investigate cerebral blood flow in the hyperacute phase (between ES/ESs and LSs) using ASL in patients with AESD.MethodsEight ASL images were acquired in six patients with AESD admitted to our hospital from October 2021 to October 2022. ASL findings in the hyperacute phase were investigated and video-electroencephalogram findings obtained around ASL image acquisition in the hyperacute phase were evaluated.ResultsFour ASL images were obtained for three patients before LS onset, with three images showing hyperperfusion areas and one image showing hypoperfusion areas. These hyperperfuion regions coincided with BTA on subsequent images of these patients.In one patient, the first ASL image was obtained in the late hyperacute phase and revealed hyperperfusion areas with a slightly abnormal change on diffusion-weighted image (DWI), which were not accompanied by ADC abnormalities. The second ASL image obtained 51 h after the first ASL, and before LS onset revealed more prominent hyperperfusion areas than the first ASL image, which were accompanied by BTA. In another patient, the ASL image obtained 82 h after ES revealed hyperperfusion areas without abnormal change on DWI or ADC.ConclusionThis study revealed that two patients exhibited hyperperfusion regions and another patient exhibited hypoperfusion regions among three patients who underwent ASL imaging during the period from 24 h after ES/ESs to LSs in patients with LSs or cooling initiation in patients without LSs due to early anaesthesia induction (late hyperacute phase). Further prospective studies on cerebral blood flow are required to explore the relationship among the timing of image acquisition, the presence of electrographic seizures, and ASL findings in patients with AESD

Immediate remote ischemic postconditioning after hypoxia ischemia in piglets protects cerebral white matter but not grey matter

Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. Our aim was to assess whether RIPostC is protective following cerebral hypoxia-ischemia in a piglet model of neonatal encephalopathy (NE) using magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry. After hypoxia-ischemia (HI), 16 Large White female newborn piglets were randomized to: (i) no intervention (n = 8); (ii) RIPostC - with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (n = 8). RIPostC reduced the hypoxic-ischemic-induced increase in white matter proton MRS lactate/N acetyl aspartate (p = 0.005) and increased whole brain phosphorus-31 MRS ATP (p = 0.039) over the 48 h after HI. Cell death was reduced with RIPostC in the periventricular white matter (p = 0.03), internal capsule (p = 0.002) and corpus callosum (p = 0.021); there was reduced microglial activation in corpus callosum (p = 0.001) and more surviving oligodendrocytes in corpus callosum (p = 0.029) and periventricular white matter (p = 0.001). Changes in gene expression were detected in the white matter at 48 h, including KATP channel and endothelin A receptor. Immediate RIPostC is a potentially safe and promising brain protective therapy for babies with NE with protection in white but not grey matter

Frequent Gene Amplification Predicts Poor Prognosis in Gastric Cancer

Gastric cancer is one of the most common malignancies worldwide. However, genetic alterations leading to this disease are largely unknown. Gene amplification is one of the most frequent genetic alterations, which is believed to play a major role in the development and progression of gastric cancer. In the present study, we identified three frequently amplified genes from 30 candidate genes using real-time quantitative PCR method, including ERBB4, C-MET and CD44, and further explored their association with clinicopathological characteristics and poor survival in a cohort of gastric cancers. Our data showed amplification of these genes was significantly associated with certain clinicopathological characteristics, particularly tumor differentiation and cancer-related death. More importantly, amplification of these genes was significantly related to worse survival, suggesting that these amplified genes may be significant predictors of poor prognosis and potential therapeutic targets in gastric cancer. Targeting these genes may thus provide new possibilities in the treatment of gastric cancer

Strong one-neutron emission from two-neutron unbound states in β decays of the r -process nuclei Ga 86,87

β-delayed one-neutron and two-neutron branching ratios (P1n and P2n) have been measured in the decay of A=84 to 87 Ga isotopes at the Radioactive-Isotope Beam Factory (RIBF) at the RIKEN Nishina Center using a high-efficiency array of He3 neutron counters (BRIKEN). Two-neutron emission was observed in the decay of Ga84,85,87 for the first time and the branching ratios were measured to be P2n=1.6(2)%,1.3(2)%, and 10.2(28)stat(5)sys%, respectively. One-neutron branching ratio of Ga87(P1n=81(9)stat(8)sys%) and half-life of 29(4) ms were measured for the first time. The branching ratios of Ga86 were also measured to be P1n=74(2)stat(8)sys% and 16.2(9)stat(6)sys% with better precision than a previous study. The observation that P1n>P2n for both Ga86,87 was unexpected and is interpreted as a signature of dominating one-neutron emission from the two-neutron unbound excited states in Ge86,87. In order to interpret the experimental results, shell-model and Hauser-Feshbach statistical model calculations of delayed particle and γ-ray emission probabilities were performed. This model framework reproduces the experimental results. The shell model alone predicts P2n significantly larger than P1n for the Ga87 decay, and it is necessary to invoke a statistical description to successfully explain the observation that P1n>P2n. Our new results demonstrate the relevance and importance of a statistical description of neutron emission for the prediction of the decay properties of multineutron emitters and that it must be included in the r-process modeling

Integrated Analyses of Copy Number Variations and Gene Expression in Lung Adenocarcinoma

Numerous efforts have been made to elucidate the etiology and improve the treatment of lung cancer, but the overall five-year survival rate is still only 15%. Identification of prognostic biomarkers for lung cancer using gene expression microarrays poses a major challenge in that very few overlapping genes have been reported among different studies. To address this issue, we have performed concurrent genome-wide analyses of copy number variation and gene expression to identify genes reproducibly associated with tumorigenesis and survival in non-smoking female lung adenocarcinoma. The genomic landscape of frequent copy number variable regions (CNVRs) in at least 30% of samples was revealed, and their aberration patterns were highly similar to several studies reported previously. Further statistical analysis for genes located in the CNVRs identified 475 genes differentially expressed between tumor and normal tissues (p<10−5). We demonstrated the reproducibility of these genes in another lung cancer study (p = 0.0034, Fisher's exact test), and showed the concordance between copy number variations and gene expression changes by elevated Pearson correlation coefficients. Pathway analysis revealed two major dysregulated functions in lung tumorigenesis: survival regulation via AKT signaling and cytoskeleton reorganization. Further validation of these enriched pathways using three independent cohorts demonstrated effective prediction of survival. In conclusion, by integrating gene expression profiles and copy number variations, we identified genes/pathways that may serve as prognostic biomarkers for lung tumorigenesis

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)