Endocrine treatment is recommended by clinical guidelines as the preferred treatment option for premenopausal as well as postmenopausal women with hormone receptor-positive, HER2-negative metastatic ...breast cancer. In real-world clinical practice, however, a substantial number of patients are treated with chemotherapy. We aimed to compare the clinical antitumour activity and safety of palbociclib plus endocrine therapy with that of capecitabine chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.
This multicentre, open-label, randomised, phase 2 study was done in 14 academic institutions in South Korea. Premenopausal women aged 19 years or older with hormone receptor-positive, HER2-negative breast cancer that had relapsed or progressed during previous tamoxifen therapy and with an Eastern Cooperative Oncology Group performance status of 0–2 were included. One line of previous chemotherapy for metastatic breast cancer was allowed. Patients were randomly assigned, using a random permuted block design (with a block size of two), to receive palbociclib plus combination endocrine therapy (oral exemestane 25 mg per day for 28 days and oral palbociclib 125 mg per day for 21 days every 4 weeks plus leuprolide 3·75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks). Randomisation was stratified by previous chemotherapy for metastatic breast cancer and visceral metastasis. The primary endpoint was progression-free survival. All analyses were done in a modified intention-to-treat population that excluded patients who did not receive study medication. This study is registered with ClinicalTrials.gov, NCT02592746, and is ongoing for follow-up of overall survival.
Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled, of whom 184 were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92). Six patients in the capecitabine group withdrew from the study before drug administration; therefore, 92 patients in the palbociclib plus endocrine therapy group and 86 patients in the capecitabine group were included in the modified intention-to-treat analyses. 46 (50%) of 92 patients in the palbociclib plus endocrine therapy group and 45 (51%) of 92 in the capecitabine group were treatment naive for metastatic breast cancer. During a median follow-up of 17 months (IQR 9–22), median progression-free survival was 20·1 months (95% CI 14·2–21·8) in the palbociclib plus endocrine therapy group versus 14·4 months (12·1–17·0) in the capecitabine group (hazard ratio 0·659 95% CI 0·437–0·994, one-sided log-rank p=0·0235). Treatment-related grade 3 or worse neutropenia was more common in the palbociclib plus endocrine therapy group than in the capecitabine group (69 75% of 92 vs 14 16% of 86 patients). 2 (2%) patients in the palbociclib plus endocrine therapy group and 15 (17%) patients in the capecitabine group had treatment-related serious adverse events. No treatment-related deaths occurred.
Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen.
Pfizer, Shinpoong, and Daewoong Korea and Takeda.
Layered low‐dimensional perovskite structures employing bulky organic ammonium cations have shown significant improvement on stability but poorer performance generally compared to their 3D ...counterparts. Here, a mixed passivation (MP) treatment is reported that uses a mixture of bulky organic ammonium iodide (iso‐butylammonium iodide, iBAI) and formammidinium iodide (FAI), enhancing both power conversion efficiency and stability. Through a combination of inactivation of the interfacial trap sites, characterized by photoluminescence measurement, and formation of an interfacial energetic barrier by which ionic transport is reduced, demonstrated by Kelvin probe force microscopy, MP treatment of the perovskite/hole transport layer interface significantly suppresses photocurrent hysteresis. Using this MP treatment, the champion mixed‐halide perovskite cell achieves a reverse scan and stabilized power conversion efficiency of 21.7%. Without encapsulation, the devices show excellent moisture stability, sustaining over 87% of the original performance after 38 d storage in ambient environment under 75 ± 20% relative humidity. This work shows that FAI/iBAI, is a new and promising material combination for passivating perovskite/selective‐contact interfaces.
Mixed passivation treatment using iso‐butylammonium iodide and formammidinium iodide applied on the surface of perovskite is shown to reduce defects and ion migration. This results in enhancement in both stability and power conversion efficiency reaching 21.7%.
Summary Acute upper gastrointestinal bleeding is a common medical emergency worldwide, a major cause of which are bleeding peptic ulcers. Endoscopic treatment and acid suppression with proton-pump ...inhibitors are cornerstones in the management of the disease, and both treatments have been shown to reduce mortality. The role of emergency surgery continues to diminish. In specialised centres, radiological intervention is increasingly used in patients with severe and recurrent bleeding who do not respond to endoscopic treatment. Despite these advances, mortality from the disorder has remained at around 10%. The disease often occurs in elderly patients with frequent comorbidities who use antiplatelet agents, non-steroidal anti-inflammatory drugs, and anticoagulants. The management of such patients, especially those at high cardiothrombotic risk who are on anticoagulants, is a challenge for clinicians. We summarise the published scientific literature about the management of patients with bleeding peptic ulcers, identify directions for future clinical research, and suggest how mortality can be reduced.
The microbiota-gut-brain axis has been suggested to play an important role in Parkinson's disease (PD). Here we performed a cross-sectional study to profile gut microbiota across early PD, REM sleep ...behavior disorder (RBD), first-degree relatives of RBD (RBD-FDR), and healthy controls, which could reflect the gut-brain staging model of PD. We show gut microbiota compositions are significantly altered in early PD and RBD compared with control and RBD-FDR. Depletion of butyrate-producing bacteria and enrichment of pro-inflammatory Collinsella have already emerged in RBD and RBD-FDR after controlling potential confounders including antidepressants, osmotic laxatives, and bowel movement frequency. Random forest modelling identifies 12 microbial markers that are effective to distinguish RBD from control. These findings suggest that PD-like gut dysbiosis occurs at the prodromal stages of PD when RBD develops and starts to emerge in the younger RBD-FDR subjects. The study will have etiological and diagnostic implications.
We conducted a population-based retrospective cohort study to investigate the influence of hospital volume, delay of surgery, and both together on the long-term survival of postoperative cancer ...patients.
Using information from the Korea Central Cancer Registry from 2001 through 2005 and the National Health Insurance claim database, we determined survival for 147 682 patients who underwent definitive surgery for any of six cancers.
Regardless of cancer site, surgical patients in low- to medium-volume hospitals showed significantly worse survival adjusted hazard ratio (aHR) = 1.36–1.86 than those in high-volume hospitals in multivariable analyses. Among the latter, treatment delays > 1 month were not associated with worse survival for stomach, colon, pancreatic, or lung cancer but were for rectal aHR = 1.28; 95% confidence interval (CI), 1.17–1.40 and breast (aHR = 1.59; 95% CI, 1.37–1.84) cancer. For patients in low- to medium-volume hospitals, treatment delay was associated with worse survival for all types of cancer (aHR = 1.78–3.81).
Our findings suggest that the effect of hospital volume and surgical treatment delay on overall survival of cancer patients should be considered in formulating or revising national health policy.
There is a growing interest in the role of timing of daily behaviors in improving health. However, little is known about the optimal timing of physical activity to maximize health benefits. We ...perform a cohort study of 92,139 UK Biobank participants with valid accelerometer data and all-cause and cause-specific mortality outcomes, comprising over 7 years of median follow-up (638,825 person-years). Moderate-to-vigorous intensity physical activity (MVPA) at any time of day is associated with lower risks for all-cause, cardiovascular disease, and cancer mortality. In addition, compared with morning group (>50% of daily MVPA during 05:00-11:00), midday-afternoon (11:00-17:00) and mixed MVPA timing groups, but not evening group (17:00-24:00), have lower risks of all-cause and cardiovascular disease mortality. These protective associations are more pronounced among the elderly, males, less physically active participants, or those with preexisting cardiovascular diseases. Here, we show that MVPA timing may have the potential to improve public health.
For the fabrication of perovskite solar cells (PSCs) using a solution process, it is essential to understand the characteristics of the perovskite precursor solution to achieve high performance and ...reproducibility. The colloids (iodoplumbates) in the perovskite precursors under various conditions were investigated by UV–visible absorption, dynamic light scattering, photoluminescence, and total internal reflection fluorescence microscopy techniques. Their local structure was examined by in situ X-ray absorption fine structure studies. Perovskite thin films on a substrate with precursor solutions were characterized by transmission electron microscopy, X-ray diffraction analysis, space-charge-limited current, and Kelvin probe force microscopy. The colloidal properties of the perovskite precursor solutions were found to be directly correlated with the defect concentration and crystallinity of the perovskite film. This work provides guidelines for controlling perovskite films by varying the precursor solution, making it possible to use colloid-engineered lead halide perovskite layers to fabricate efficient PSCs.
Organic-inorganic metal halide perovskites have gained considerable attention for next-generation photovoltaic cells due to rapid improvement in power conversion efficiencies. However, fundamental ...understanding of underlying mechanisms related to light- and bias-induced effects at the nanoscale is still required. Here, structural variations of the perovskites induced by light and bias are systematically investigated using scanning probe microscopy techniques. We show that periodically striped ferroelastic domains, spacing between 40 to 350 nm, exist within grains and can be modulated significantly under illumination as well as by electric bias. Williamson-Hall analysis of X-ray diffraction results shows that strain disorder is induced by these applied external stimuli. We show evidence that the structural emergence of domains can provide transfer pathways for holes to a hole transport layer with positive bias. Our findings point to potential origins of I-V hysteresis in halide perovskite solar cells.
Metal halide perovskite solar cells (PSCs) have undergone rapid progress. However, unstable performance caused by sensitivity to environmental moisture and high temperature is a major impediment to ...commercialization of PSCs. In the present work, a low-temperature, glass–glass encapsulation technique using high performance polyisobutylene (PIB) as the moisture barrier is investigated on planar glass/FTO/TiO2/FAPbI3/PTAA/gold perovskite solar cells. PIB was applied as either an edge seal or blanket layer. Electrical connections to the encapsulated PSCs were provided by either the FTO or Au layers. Results of a “calcium test” demonstrated that a PIB edge-seal effectively prevents moisture ingress. A shelf life test was performed and the PIB-sealed PSC was stable for at least 200 days. Damp heat and thermal cycling tests, in compliance with IEC61215:2016, were used to evaluate different encapsulation methods. Current–voltage measurements were performed regularly under simulated AM1.5G sunlight to monitor changes in PCE. The best results we have achieved to date maintained the initial efficiency after 540 h of damp heat testing and 200 thermal cycles. To the best of the authors’ knowledge, these are among the best damp heat and thermal cycle test results for perovskite solar cells published to date. Given the modest performance of the cells (8% averaged from forward and reverse scans) especially with the more challenging FAPbI3 perovskite material tested in this work, it is envisaged that better stability results can be further achieved when higher performance perovskite solar cells are encapsulated using the PIB packaging techniques developed in this work. We propose that heat rather than moisture was the main cause of our PSC degradation. Furthermore, we propose that preventing the escape of volatile decomposition products from the perovskite solar cell materials is the key for stability. PIB encapsulation is a very promising packaging solution for perovskite solar cells, given its demonstrated effectiveness, ease of application, low application temperature, and low cost.
Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to ...disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.
In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.
Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as
,
and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.
Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
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