The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum‐based chemotherapy in patients with resected stage IB–IIIA non‐small cell lung ...cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)–IIIA NSCLC. Upon completing 1–4 cycles of adjuvant cisplatin‐based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator‐assessed disease‐free survival, tested hierarchically first in patients with stage II–IIIA NSCLC whose tumors expressed programmed death‐ligand 1 (PD‐L1) on ≥1% of tumor cells, then in all randomized patients with stage II–IIIA NSCLC, and finally in the intention‐to‐treat (ITT) population (stage IB–IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all‐randomized stage II–IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD‐L1 tumor cells ≥1% stage II–IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease‐free survival improvement with atezolizumab vs BSC was observed in the PD‐L1 tumor cells ≥1% stage II–IIIA (unstratified hazard ratio HR, 0.52; 95% confidence interval CI, 0.25–1.08), all‐randomized stage II–IIIA (unstratified HR, 0.62; 95% CI, 0.35–1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34–1.10) populations. Atezolizumab‐related grade 3/4 adverse events occurred in 16% of patients; no treatment‐related grade 5 events occurred. Adjuvant atezolizumab showed disease‐free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
This manuscript reports a subgroup analysis of Japanese patients in the global phase 3 IMpower010 study evaluating adjuvant atezolizumab vs best supportive care (BSC) following platinum‐based chemotherapy in resected stage IB‐IIIA non‐small cell lung cancer. Disease‐free survival (DFS) improvement with atezolizumab versus BSC was observed in the Japanese stage II‐IIIA population with PD‐L1 expression on ≥1% of tumor cells; in the Japanese all‐randomized stage II‐IIIA and ITT (stage IB‐IIIA) populations, unstratified DFS hazard ratios favored atezolizumab vs BSC. Adjuvant atezolizumab had a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
In the global phase III IMpassion031 study, neoadjuvant atezolizumab plus nab-paclitaxel/anthracycline-based chemotherapy improved pathological complete response in patients with ...early stage triple-negative breast cancer. Here, we report primary analysis results from a subgroup of Japanese patients.
Methods
Patients with histologically documented, previously untreated, stage cT2–cT4, cN0–cN3, cM0 triple-negative breast cancer were randomized 1:1 to receive intravenous atezolizumab 840 mg or placebo every 2 weeks in combination with chemotherapy consisting of nab-paclitaxel intravenous 125 mg/m2 once a week, followed by doxorubicin intravenous 60 mg/m2 and cyclophosphamide intravenous 600 mg/m2 every 2 weeks. Patients then underwent surgery. Pathological complete response (ypT0/is ypN0) in the intention-to-treat and PD-L1-positive (≥1% PD-L1-expressing tumor-infiltrating immune cells) populations were co-primary endpoints.
Results
This subanalysis (data cutoff: 3 April 2020) included 36 patients from Japan (intention-to-treat; atezolizumab arm, n = 17; placebo arm, n = 19). Pathological complete response occurred in 41% (n = 7; 95% confidence interval, 18–67) of patients in the atezolizumab arm and 37% (n = 7; 95% confidence interval, 16–62) in the placebo arm. In the PD-L1-positive population, pathological complete response occurred in 50% (n = 5; 95% confidence interval, 19–81) of patients in the atezolizumab arm and 45% (n = 5; 95% confidence interval, 17–77) in the placebo arm. Treatment-related grade 3–4 adverse events occurred in 71% and 68% of patients in the respective arms.
Conclusion
Atezolizumab added to neoadjuvant chemotherapy numerically improved pathological complete response versus placebo in this small exploratory analysis of Japanese patients with early stage triple-negative breast cancer, a trend directionally consistent with the global study results. No new safety signals were identified.
Vascular dysfunction and injurious stimuli such as oxidative stress are closely related to the risk of cardiovascular diseases (CVD). Dietary polyphenols are reported to exert beneficial effects in ...reducing the risk of CVD. Black soybean has been used as a nutritionally rich food and contains abundant polyphenols in its seed coat and grain. Black soybean has many beneficial physiological activities, and its prevention effects on CVD risk were reported mainly in animal experiments. In this study, we performed a randomized, single blind, placebo controlled, crossover trial to investigate the effect of black soybean consumption on the vascular function in healthy humans. Twenty-two healthy adults aged from 30 to 60 completed the four week trial with daily consumption of about a 40 g test material cookie containing 20 g roasted black soybean powder. Body composition, vascular function, biomarkers for oxidative stress, and polyphenol contents in the urine and the plasma were measured. After ingestion of the black soybean cookie, vascular function, which was evaluated by plethysmogram using a Pulse Analyzer
, was improved and systolic blood pressure was decreased. Moreover, nitric oxide levels in plasma and urine were increased, while an oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine level, in the plasma was decreased accompanied by an increase in the concentration of polyphenols derived from black soybean in plasma and urine. These results suggest that the antioxidant activity of black soybean polyphenols and an increase in the nitric oxide level may contribute to the improvement of vascular function. Thus, black soybean is an attractive food material for improvement of vascular function through decreasing oxidative stress by its potent antioxidant activity and increasing the nitric oxide level in healthy humans.
With the increasing popularity of selective lamellar keratoplasty procedures, it is important to characterize the optical differences among penetrating keratoplasty (PK), deep anterior lamellar ...keratoplasty (DALK), and Descemet stripping automated endothelial keratoplasty (DSAEK). The impact of optical differences on the visual acuity (VA) in eyes after keratoplasty is significant. Quantitative evaluation of corneal higher-order aberrations (HOAs) of anterior and posterior surfaces using a rotating Scheimpflug-based corneal topographer, showed that eyes that undergo DSAEK have lower anterior corneal HOAs compared with eyes subjected to PK or DALK. In DSAEK, the anterior corneal surfaces are not replaced, which is in contrast to PK or DALK, where they are replaced. Through evaluation of corneal scatter with a densitometry program associated with the rotating Scheimpflug-based corneal topographer, 3 characteristic patterns of corneal scatter were found in eyes that had undergone keratoplasty. Investigation of the impact of corneal HOAs and corneal scatter on VA after keratoplasty showed that the VA was correlated significantly with corneal scatter.
Methotrexate (MTX) is widely used as an anchor drug for the treatment of rheumatoid arthritis (RA) because of its ability to control pain and inflammation. However, few studies have shown that ...long-term MTX use can lead to lymphoproliferative disorders (LPDs) in these patients. Here we describe a rare case of intracranial MTX-associated LPD in a patient with RA.
A 68-year-old woman was admitted to our hospital because of progressive right limb palsy. She was diagnosed with RA 15 years ago and has been receiving MTX therapy for the past 5 years. Magnetic resonance imaging of the head revealed a ring-enhancing lesion in the left parietal lobe. Open biopsy was performed for making a definite diagnosis and planning treatment. Hematoxylin-eosin stain revealed dense proliferation of atypical lymphocytes in the perivascular lesion. Immunohistochemistry results were positive for CD20; this lesion was observed as a strong nuclear signal on in-situ hybridization for the Epstein-Barr virus-encoded RNA. Finally, the patient was diagnosed with MTX-associated LPD. We discontinued MTX administration and initiated steroid therapy for RA. The intracranial lesion reduced in size, and her symptoms resolved after MTX discontinuation; no recurrence has been observed at 3 years after MTX discontinuation.
Intracranial MTX-associated LPD is extremely rare. Here we describe a particular case and review the literature pertaining to intracranial MTX-associated LPD. More attention should be paid to LPD in a patient receiving immunosuppressive treatment for RA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Decomposition product of 1,2-bis(2-methyl-1-benzofuran-3-yl)ethene is identified.•The amount of the product increases with time duration of heating at 100 °C.•This compound is a ...product of oxidation in air.•The DFT calculation of the product is conducted to reveal the absorption spectrum.
1,2-Bis(2-methyl-1-benzofuran-3-yl)perfluorocyclopentene shows photochromism in n-hexane at room temperature. We have identified a new compound produced by the thermal decomposition in a mixture of cis- and trans-decahydronaphthalene above 100 °C in the absence of light.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Background
Autistic people demonstrate focused interests, sensitivity to sensory stimulation, and, compared with the general population, differences in social communication and interaction. ...We examined whether a combination of the Awareness and Care for My Autistic Traits (ACAT) program and treatment-as-usual is more effective than only treatment-as-usual in increasing the understanding of autistic attributes, reducing treatment stigma, and improving mental health and social adaptation among autistic adolescents and their parents/guardians.
Methods
Forty-nine adolescents and their parents/guardians were randomly assigned to either a combination of ACAT and treatment-as-usual or only treatment-as-usual. The combined group received six weekly 100-minute ACAT sessions, while the treatment-as-usual group received no additional intervention. The primary outcome was the change in understanding of autistic attributes (Autism Knowledge Quiz-Child), administered from pre- to post-intervention. The secondary outcomes included the change in Autism Knowledge Quiz-Parent, reduced treatment stigma, and improved mental health and social adaptation among autistic adolescents and their parents/guardians. A primary outcome measure scale was scored by assessors who were blind to the group assignment.
Results
The combined group (both autistic adolescents and their parents/guardians) showed an increase in Autism Knowledge Quiz scores compared to those in the treatment-as-usual group. Autistic adolescents in the combined group also demonstrated a decrease in treatment-related stigma and an improvement in general mental health compared to those in the treatment-as-usual group, while there were no group differences in the change in social adaptation. For parents/guardians, there were no group differences in the change in treatment-related stigma, general mental health, adaptive skills, or attitudes toward their children.
Conclusions
The ACAT program could be an effective treatment modality to increase the understanding of autistic attributes among both autistic adolescents and their parents/guardians. The ACAT program positively affects self-understanding, reduces treatment stigma, and stabilizes behavioral issues for autistic adolescents as a part of mental health measures, but it does not effectively reduce treatment barriers or improve mental health for parents/guardians. Further research should consider whether additional support for parents/guardians could be beneficial.
Trial registration
: The study was registered in UMIN (UMIN000029851, 06/01/2018).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Vascular dysfunction and injurious stimuli such as oxidative stress is closely related to the risk of cardiovascular diseases (CVD). Dietary polyphenols is reported to exert the beneficial effects on ...reducing the risk of CVD. Black soybean is rich in polyphenols, including isoflavones, anthocyanidins and flavan-3-ols, and its prevention effects on CVD risk were reported in the animal experiments. In this study, we investigated the effect of black soybean consumption on the vascular function and oxidative stress associating with the polyphenol concentrations in healthy women. Lowered vascular age was observed in 33 out of 44 volunteers who completed the 8-week trial. It was observed that improvement of the vascular stiffness, increasing in the urinary NO2 and NO3 level, and decreasing in the oxidative stress markers, 8-hydroxy-2′-deoxyguanosine, hexanoyl-lysine and myeloperoxidase. In addition, concentration of 12 polyphenols in black soybean increased in the plasma and urine. Increased concentration of polyphenols would be involved in the decreased oxidative stress. Thus, black soybean consumption improved the vascular function through an increase in nitric oxide and a decrease in oxidative stress accompanied by increasing the polyphenol concentrations in healthy women.
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•Black soybean improves vascular function in healthy women.•Black soybean increases nitric oxide concentration and decreases oxidative stress markers.•Black soybean polyphenols are involved in the improvement of vascular function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Highlights•Sabin-derived IPV was introduced to routine immunization in Japan in 2012. •Seroprevalence of poliovirus antibody was examined after IPV introduction in Japan. •Polio vaccination coverage ...in children remained high even after IPV introduction. •Seropositivity rates for poliovirus in children increased after IPV introduction. •Seropositivity rates for all 3 types were high in children receiving IPV.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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