Immune checkpoint inhibitors (ICIs) are indicated for various cancers and are the mainstay of cancer immunotherapy. They are often associated with ICI-related pneumonitis (CIP), however, hindering a ...favorable clinical course. Recently, non-oncology concomitant drugs have been reported to affect the efficacy and toxicity of ICIs; however, the association between these drugs and the risk for CIP is uncertain. The aim of this study was to assess the impact of baseline concomitant drugs on CIP incidence in ICI-treated advanced cancer patients.
This was a single-center retrospective study that included a cohort of 511 patients with advanced cancer (melanoma and non-small-cell lung, head and neck, genitourinary, and other types of cancer) treated with ICIs. Univariable analysis was conducted to identify baseline co-medications associated with CIP incidence. A propensity score matching analysis was used to adjust for potential CIP risk factors, and multivariable analysis was carried out to assess the impact of the identified co-medications on CIP risk.
Forty-seven (9.2%) patients developed CIP. In these patients, the organizing pneumonia pattern was the dominant radiological phenotype, and 42.6% had grade ≥3 CIP, including one patient with grade 5. Of the investigated baseline co-medications, the proportion of antiplatelet drugs (n = 50, 9.8%) was higher in patients with CIP (23.4% versus 8.4%). After propensity score matching, the CIP incidence was higher in patients with baseline antiplatelet drugs (22% versus 6%). Finally, baseline antiplatelet drug use was demonstrated to increase the risk for CIP incidence regardless of cancer type (hazard ratio, 3.46; 95% confidence interval 1.21-9.86).
An association between concomitant antiplatelet drug use at baseline and an increased risk for CIP was seen in our database. This implies the importance of assessing concomitant medications for CIP risk management.
•We studied the association between baseline drugs and CIP in ICI-treated advanced cancer patients with multiple cancer types.•Baseline antiplatelet drugs were associated with an increased risk for CIP incidence (HR, 3.46; 95% CI 1.21-9.86).•This study suggested the importance of evaluating concomitant drugs for CIP risk stratification in ICI therapy.
High-resolution X-ray spectroscopy of the highly charged muonic atoms/ions isolated in vacuum is an ideal probe to explore quantum electrodynamics under extremely strong electric fields, which is one ...of the major topic in fundamental atomic physics. A feasibility test measurement with a low-density neon gas target was performed by observing X-rays emitted by muonic neon via the
5
→
4
transition,
∼
6.3 keV, using a multi-pixel array of superconducting transition-edge-sensor (TES) microcalorimeters at the J-PARC muon facility. We successfully demonstrated the feasibility of muonic atom X-ray spectroscopy with a gas target at a pressure as low as 0.1 atom using TES array under an intense pulsed muon beam.
Aims: To describe the clinical and histopathological findings in a patient with polypoidal choroidal vasculopathy. Methods: A 76 year old Japanese man had a discrete, orange-red lesion of 1 disc ...diameter in the macula, with the fluorescein and indocyanine green angiographic and optical coherence tomographic findings compatible with polypoidal choroidal vasculopathy. He underwent a surgical removal of the macular lesion, followed by light and electron microscopic examinations. Results: The histopathological examination revealed that the specimen consisted of degenerated retinal pigment epithelium-Bruch’s membrane-choriocapillaris complex and inner choroid. A tortuous, unusually dilated venule was present adjacent to an arteriole with marked sclerotic changes, appearing to form arteriovenous crossing. These vessels seemed to represent native inner choroidal vessels, and had haemorrhage per diapedesis. Blood cells and fibrin filled the lumina of the vessels and accumulated in the extravascular spaces, indicating vascular stasis. Conclusion: Hyperpermeability and haemorrhage due to stasis of a dilated venule and an arteriole involved by sclerosis at the site where they cross in the inner choroid might cause oedema and degeneration of the tissue. Voluminous accumulation of blood cells and fibrin might generate elevation of tissue pressure sufficient to displace the weakened lesion anteriorly. The result suggests that the polypoidal vessels in this case represent abnormality in the inner choroidal vasculature.
MuSEUM (Muonium Spectroscopy Experiment Using Microwave) collaboration aims to measure the muonium hyperfine structure (MuHFS,vhfs) with a few ppb (parts per billion). MuHFS spectroscopy is a ...stringent test of the bound-state QED. From this measurement, the muon-proton magnetic moment ratio (μμ/μP) and the muon-electron mass ratio (mμ/me) can also be determined by applying a high magnetic field. In the previous MuHFS measurement carried out at Los Alamos Meson Physics Facility (LAMPF), the main uncertainty was caused by the lack of the statistics. MuSEUM collaboration uses the high intense pulsed muon beam at Japan Proton Accelerator Research Complex (J-PARC) to improve the statistical uncertainty. We are also developing our own experimental setups for the improvement of the systematic uncertainties. From June 2016, MuSEUM collaboration have carried out the MuHFS measurement in an extremely low magnetic field within 100 nT and now we are preparing for the measurement in a 1.7 T high magnetic field.
Lymph node dissemination is a major prognostic factor in human cancer. However, the molecular mechanisms underlying lymph node metastasis are poorly understood. Recently, vascular endothelial growth ...factor-C (VEGF-C) was identified as a ligand for VEGF receptor-3 (VEGFR-3/Flt-4) and the expression of VEGFR-3 was found to be highly restricted to the lymphatic endothelial cells. In this report, we investigated the expression of VEGF-C and VEGFR-3 in human prostatic carcinoma tissue by using in situ hybridization and immunohistochemical staining respectively. Expression of VEGF-C mRNA in prostatic carcinoma was significantly higher in lymph node-positive group than in lymph node-negative group. In addition, the number of VEGFR-3-positive vessels was increased in stroma surrounding VEGF-C-positive prostatic carcinoma cells. These results suggest that the expression of VEGF-C in prostatic carcinoma cells is implicated in the lymph node metastasis.
We developed a new positron detector system called Kalliope, which is based on multi-pixel avalanch photo-diode (m-APD), application specific integrated circuit (ASIC), field programmable gated array ...(FPGA) and ethernet-based SiTCP data transfer technology. We have manufactured a general-purpose spectrometer for muon spin relaxation (μSR) measurements, employing 40 Kalliope units (1280 channels of scintillators) installed in a 0.4 T longitudinal-field magnet. The spectrometer has been placed at D1 experimental area of J- PARC Muon Science Establishment (MUSE). Since February of 2014, the spectrometer has been used for the user programs of MUSE after a short commissioning period of one week. The data accumulation rate of the new spectrometer is 180 million positron events per hour (after taking the coincidence of two scintillators of telescopes) from a 20×20 mm sample for double-pulsed incoming muons.
At the Muon Science Facility (MUSE) of J-PARC (Japan Proton Accelerator Research Complex), the MuSEUM collaboration is planing new measurements of the ground state hyperfine structure (HFS) of ...muonium both at zero field and at high magnetic field. The previous measurements were performed both at LAMPF (Los Alamos Meson Physics Facility) with experimental uncertainties mostly dominated by statistical errors. The new high intensity muon beam that will soon be available at MUSE H-Line will provide an opportunity to improve the precision of these measurements by one order of magnitude. An overview of the different aspects of these new muonium HFS measurements, the current status of the preparation, and the results of a first commissioning test experiment at zero field are presented.
The objective of this study was to investigate the effect of dietary supplementation with the disaccharides trehalose and cellobiose on antioxidant activity in rumen fluid, blood, and milk of dairy ...cows. Nine Holstein dairy cows housed in a free-stall barn were divided into 3 groups, with each group receiving a different dietary treatment (a control diet, a 1% trehalose-supplemented diet, or a 1% cellobiose-supplemented diet) following a 3 × 3 Latin square design. Feed intake and milk production increased in cows receiving the trehalose-supplemented diet compared with those receiving the control and cellobiose-supplemented diets. The total protozoa numbers in the rumen fluid of cows fed trehalose- or cellobiose-supplemented diets were greater than those of the control group. The C18:0 and C18:1 fatty acid content was increased in the milk of cows fed the trehalose-supplemented diet compared with that of the control group, and the C18:3n-3 fatty acid content in the milk of cows fed the cellobiose-supplemented diet was less than that of the control group. Plasma biochemical parameters were unchanged among the different treatments. In rumen fluid, 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and superoxide dismutase activity were increased 2h after feeding in cows receiving the cellobiose-supplemented diet compared with the control group, and the concentration of thiobarbituric acid reactive substances in the rumen fluid of cows fed the cellobiose-supplemented diet was decreased. In contrast, the values of these parameters measured in the milk of cows fed the cellobiose-supplemented diet were no different from those of control cows. Dietary supplementation with trehalose did, however, bring about an improvement of the oxidative status of milk and blood in these animals compared with controls. These results provide the first evidence supporting the use of dietary disaccharides to decrease lipid peroxide levels and increase the antioxidant content of dairy cow milk. The findings suggest that disaccharides, particularly trehalose, might be useful as supplements for reducing oxidative stress and improving the quality of milk for human consumption, as well as possibly impairing the processes that give rise to lipid oxidation odor in dairy cow milk.
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