36 research outputs found
A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part
This multicenter, double-blind, phase 2a part of a phase 2/3 study assessed the efficacy and safety of ensitrelvir, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor, in Japanese patients with mild-to-moderate coronavirus disease 2019 (COVID-19) or asymptomatic ARSCoV- 2 infection. Sixty-nine patients were randomized (1:1:1) to orally receive 5-day ensitrelvir fumaric acid (375 mg on day 1 followed by 125 mg daily, or 750 mg on day 1 followed by 250 mg daily) or placebo and followed up until day 28. The primary outcome was the change from baseline in the SARS-CoV-2 viral titer. A total of 16, 14, and 17 patients in the ensitrelvir 125 mg, ensitrelvir 250 mg, and placebo groups, respectively, were included in the intention-to-treat population (mean age: 38.0 to 40.4 years). On day 4, the change from baseline in SARS-CoV-2 viral titer (log10 50% tissue culture infectious dose/mL) in patients with positive viral titer and viral RNA at baseline was greater with ensitrelvir 125 mg (mean [standard deviation], –2.42 [1.42]; P = 0.0712) and 250 mg (–2.81 [1.21]; P = 0.0083) versus placebo (–1.54 [0.74]); ensitrelvir treatment reduced SARS-CoV-2 RNA by –1.4 to –1.5 log10 copies/ mL versus placebo. The viral titer and viral RNA were similar across groups on and after day 6. The median time to infectious viral clearance decreased by approximately 50 h with ensitrelvir treatment. All adverse events were mild to moderate. Ensitrelvir treatment demonstrated rapid SARS-CoV-2 clearance and was well tolerated (Japan Registry of Clinical Trials identifier: jRCT2031210350)
Assessment of Outcome of Hepatic Arterial Infusion Chemotherapy in Patients with Advanced Hepatocellular Carcinoma by the Combination of RECIST and Tumor Markers
To assess the outcome of stable disease (SD) patients with advanced hepatocellular carcinoma (HCC) by tumor markers after the first course of hepatic arterial infusion chemotherapy (HAIC). The study subjects were 156 HCC patients treated with HAIC and classified as Child Pugh A, with no extrahepatic metastasis, and no history of sorafenib treatment. In the study and validation cohorts, the AFP and DCP ratios of patients who were considered SD to the first course of HAIC were analyzed by AUROC for a prediction of response to the second course of HAIC. The imaging response to the first course of HAIC was classified as partial response (PR), SD and progressive disease (PD) in 29 (18.8%), 80 (51.9%), and 44 (28.6%) patients respectively. For SD patients, the α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) ratios of patients who were considered SD to the first course of HAIC were analyzed by the receiver operating characteristic curve for prediction of response to the second course of HAIC in the study cohorts. The area under the curve of AFP ratio was 0.743. The area under the curve of DCP ratio was 0.695. The cut-off values of AFP and DCP ratios were 1.3 and 1.0, respectively. In the validation cohort, the accuracy of the prediction of response in this validation cohort (71.4%) showed no significant difference compared to that in the study cohort (72.4%) (p = 1.0). The results suggested that patients with a high tumor marker ratio could be switched to alternative therapeutic regimens despite the SD response to HAIC
Reactive Crystallization Behaviour of Calcium Phosphate with and Without Whey Protein Addition
A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part
Photo- and Vapor-Controlled Luminescence of Rhombic Dicopper(I) Complexes Containing Dimethyl Sulfoxide
Halide-bridged rhombic dicopperÂ(I)
complexes, [Cu<sub>2</sub>Â(μ-X)<sub>2</sub>Â(DMSO)<sub>2</sub>Â(PPh<sub>3</sub>)<sub>2</sub>] (X = I<sup>–</sup>, Br<sup>–</sup>; DMSO = dimethyl sulfoxide; PPh<sub>3</sub> = triphenylphosphine), were synthesized, the iodide complex of which
exhibited interesting photochromic luminescence driven by photoirradiation
and by exposure to DMSO vapor in the solid state. Single-crystal X-ray
diffraction measurements revealed that the iodo and bromo complexes
(abbreviated <b>Cu</b><sub><b>2</b></sub><b>I</b><sub><b>2</b></sub><b>-[O,O]</b> and <b>Cu</b><sub><b>2</b></sub><b>Br</b><sub><b>2</b></sub><b>-[O,O]</b>) were isomorphous, and that the two DMSO ligands were
coordinated to the CuÂ(I) ion via the O atom in both complexes. Both
complexes exhibited bright blue phosphorescence at room temperature
(λ<sub>em</sub> = 435 nm, Φ<sub>em</sub> = 0.19 and 0.14
for <b>Cu</b><sub><b>2</b></sub><b>I</b><sub><b>2</b></sub><b>-[O,O]</b> and <b>Cu</b><sub><b>2</b></sub><b>Br</b><sub><b>2</b></sub><b>-[O,O]</b>, respectively) with a relatively long emission lifetime (τ<sub>em</sub> ∼ 200 μs at 77 K) derived from the mixed halide-to-ligand
and metal-to-ligand charge transfer (<sup>3</sup>XLCT and <sup>3</sup>MLCT) excited state. Under UV irradiation, the blue phosphorescence
of <b>Cu</b><sub><b>2</b></sub><b>Br</b><sub><b>2</b></sub><b>-[O,O]</b> disappeared uneventfully and no
new emission band appeared, whereas the blue phosphorescence of <b>Cu</b><sub><b>2</b></sub><b>I</b><sub><b>2</b></sub><b>-[O,O]</b> rapidly disappeared with simultaneous appearance
of a new green emission band (λ<sub>em</sub> = 500 nm). On further
irradiation, the green emission of the iodide complex gradually changed
to bright yellowish-green (λ<sub>em</sub> = 540 nm); however,
this change could be completely suppressed by lowering the temperature
to 263 K or in the presence of saturated DMSO vapor. The initial blue
phosphorescence of <b>Cu</b><sub><b>2</b></sub><b>I</b><sub><b>2</b></sub><b>-[O,O]</b> was recovered by exposure
to DMSO vapor at 90 °C for a few hours. IR spectroscopy and theoretical
calculations suggest that the DMSO ligand underwent linkage isomerization
from O-coordination to S-coordination, and both the occurrence of
linkage isomerization and the removal of DMSO result in contraction
of the rhombic Cu<sub>2</sub>Â(μ-I)<sub>2</sub> core to
make the Cu···Cu interaction more effective. In the
contracted core, the triplet cluster-centered (<sup>3</sup>CC) emissive
state is easily generated by thermal excitation of the <sup>3</sup>XLCT and <sup>3</sup>MLCT mixed transition state, resulting in the
green to yellowish-green emission. In contrast, the Cu···Cu
distance in <b>Cu</b><sub><b>2</b></sub><b>Br</b><sub><b>2</b></sub><b>-[O,O]</b> is considerably longer
than that of <b>Cu</b><sub><b>2</b></sub><b>I</b><sub><b>2</b></sub><b>-[O,O]</b>, which destabilizes
the <sup>3</sup>CC emissive state, resulting in the nonemissive character
Photo- and Vapor-Controlled Luminescence of Rhombic Dicopper(I) Complexes Containing Dimethyl Sulfoxide
Halide-bridged rhombic dicopperÂ(I)
complexes, [Cu<sub>2</sub>Â(μ-X)<sub>2</sub>Â(DMSO)<sub>2</sub>Â(PPh<sub>3</sub>)<sub>2</sub>] (X = I<sup>–</sup>, Br<sup>–</sup>; DMSO = dimethyl sulfoxide; PPh<sub>3</sub> = triphenylphosphine), were synthesized, the iodide complex of which
exhibited interesting photochromic luminescence driven by photoirradiation
and by exposure to DMSO vapor in the solid state. Single-crystal X-ray
diffraction measurements revealed that the iodo and bromo complexes
(abbreviated <b>Cu</b><sub><b>2</b></sub><b>I</b><sub><b>2</b></sub><b>-[O,O]</b> and <b>Cu</b><sub><b>2</b></sub><b>Br</b><sub><b>2</b></sub><b>-[O,O]</b>) were isomorphous, and that the two DMSO ligands were
coordinated to the CuÂ(I) ion via the O atom in both complexes. Both
complexes exhibited bright blue phosphorescence at room temperature
(λ<sub>em</sub> = 435 nm, Φ<sub>em</sub> = 0.19 and 0.14
for <b>Cu</b><sub><b>2</b></sub><b>I</b><sub><b>2</b></sub><b>-[O,O]</b> and <b>Cu</b><sub><b>2</b></sub><b>Br</b><sub><b>2</b></sub><b>-[O,O]</b>, respectively) with a relatively long emission lifetime (τ<sub>em</sub> ∼ 200 μs at 77 K) derived from the mixed halide-to-ligand
and metal-to-ligand charge transfer (<sup>3</sup>XLCT and <sup>3</sup>MLCT) excited state. Under UV irradiation, the blue phosphorescence
of <b>Cu</b><sub><b>2</b></sub><b>Br</b><sub><b>2</b></sub><b>-[O,O]</b> disappeared uneventfully and no
new emission band appeared, whereas the blue phosphorescence of <b>Cu</b><sub><b>2</b></sub><b>I</b><sub><b>2</b></sub><b>-[O,O]</b> rapidly disappeared with simultaneous appearance
of a new green emission band (λ<sub>em</sub> = 500 nm). On further
irradiation, the green emission of the iodide complex gradually changed
to bright yellowish-green (λ<sub>em</sub> = 540 nm); however,
this change could be completely suppressed by lowering the temperature
to 263 K or in the presence of saturated DMSO vapor. The initial blue
phosphorescence of <b>Cu</b><sub><b>2</b></sub><b>I</b><sub><b>2</b></sub><b>-[O,O]</b> was recovered by exposure
to DMSO vapor at 90 °C for a few hours. IR spectroscopy and theoretical
calculations suggest that the DMSO ligand underwent linkage isomerization
from O-coordination to S-coordination, and both the occurrence of
linkage isomerization and the removal of DMSO result in contraction
of the rhombic Cu<sub>2</sub>Â(μ-I)<sub>2</sub> core to
make the Cu···Cu interaction more effective. In the
contracted core, the triplet cluster-centered (<sup>3</sup>CC) emissive
state is easily generated by thermal excitation of the <sup>3</sup>XLCT and <sup>3</sup>MLCT mixed transition state, resulting in the
green to yellowish-green emission. In contrast, the Cu···Cu
distance in <b>Cu</b><sub><b>2</b></sub><b>Br</b><sub><b>2</b></sub><b>-[O,O]</b> is considerably longer
than that of <b>Cu</b><sub><b>2</b></sub><b>I</b><sub><b>2</b></sub><b>-[O,O]</b>, which destabilizes
the <sup>3</sup>CC emissive state, resulting in the nonemissive character
A First Case of Hepatic Angiosarcoma Treated with Recombinant Interleukin-2
A 60 year-old woman was admitted to our hospital because of management of multiple liver tumors. According to image findings and liver biopsy, she was diagnosed as having epithelioid hemangioendothelioma of the liver accompanied by metastases in the spleen, lungs and bones. Based on the spread of the liver tumors and the extensive systemic metastases, she was considered inoperable. Instead, she received hepatic arterial infusion therapy using recombinant interleukin-2. However, she died due to liver failure about two months after admission. Autopsy revealed that the liver tumor was angiosarcoma. It is difficult to differentiate angiosarcoma from epithelioid hemangioendothelioma based on the image findings and pathological findings of percutaneous liver biopsy. Many cases are diagnosed as angiosarcoma at autopsy. There is no established effective treatment for hepatic angiosarcoma, because the tumor stage at the time of diagnosis is often progressive. To date, immunotherapy with recombinant interleukin-2 has been reported to be effective clinically for cutaneous angiosarcoma, such as of the scalp and facial skin. To our knowledge, there have been no reported cases of hepatic angiosarcoma treated with recombinant interleukin-2. Our case is important should recombinant interleukin-2 be considered effective for hepatic angiosarcoma in the future