Background and purpose
We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial ...fibrillation.
Methods
The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K‐ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence.
Results
Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance 103 episodes (31.3%) followed by extracranial bleeding 96 episodes (29.2%). Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2DS2‐VASc score were not significantly different between patients with and without recurrent stroke.
Conclusions
A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.
Mutation in PTEN has not yet been detected, but its function as a tumor suppressor is inactivated in many cancers. In this study we determined that, activated Notch signaling disables PTEN by ...phosphorylation and thereby contributes to gastric tumorigenesis. Notch inhibition by small interfering RNA or γ-secretase inhibitor (GSI) induced mitotic arrest and apoptosis in gastric cancer cells. Notch inhibition induced dephosphorylation in the C-terminal domain of PTEN, which led to PTEN nuclear localization. Overexpression of activated Notch1-induced phosphorylation of PTEN and reversed GSI-induced mitotic arrest. Dephosphorylated nuclear PTEN caused prometaphase arrest by interaction with the cyclin B1-CDK1 complex, resulting in their accumulation in the nucleus and subsequent apoptosis. We found a correlation between high expression levels of Notch1 and low survival rates and, similarly, between reduced nuclear PTEN expression and increasing the TNM classification of malignant tumours stages in malignant tissues from gastric cancer patients. The growth of Notch1-depleted gastric tumors was significantly retarded in xenografted mice, and in addition, PTEN deletion restored growth similar to control tumors. We also demonstrated that combination treatment with GSI and chemotherapeutic agents significantly reduced the orthotopically transplanted gastric tumors in mice without noticeable toxicity. Overall, our findings suggest that inhibition of Notch signaling can be employed as a PTEN activator, making it a potential target for gastric cancer therapy.
Aim
To investigate the relationship between small dense LDL cholesterol and cardiac autonomic neuropathy among patients with Type 2 diabetes.
Methods
A total of 175 patients who had not taken ...lipid‐lowering agents previously were enrolled consecutively in this study. Small dense LDL cholesterol level was measured using polyacrylamide tube gel electrophoresis, which fractionates LDL cholesterol into seven components according to particle size and charge. We analysed the mean LDL cholesterol particle size and the proportion of small dense LDL cholesterol.
Results
The mean (± sd) patient age was 56 (± 14) years, the mean (± sd) duration of diabetes was 10.3 (± 8.3) years, the mean (± sd) proportion of small dense LDL cholesterol was 21.3 (± 17.6)% and the mean (± sd) LDL cholesterol size was 26.33 (± 0.8) nm. Men with cardiac autonomic neuropathy had a longer duration of diabetes compared with those without cardiac autonomic neuropathy. Women with cardiac autonomic neuropathy had a larger waist circumference, higher plasma triglyceride levels, smaller mean (± sd) LDL cholesterol size 26.8 (± 4.3) nm vs 26.4 (± 6.9) nm; P < 0.01 and larger mean (± sd) proportion of small dense LDL cholesterol 10.1 (± 9.9)% vs 19.1 (± 16.8)%; P < 0.01 compared with those without cardiac autonomic neuropathy. After adjusting for other confounding risk factors, the triglyceride/ HDL cholesterol ratio (odds ratio = 1.698, 95% CI: 1.07–2.69; P = 0.025) and mean LDL cholesterol size (odds ratio = 0.873, 95% CI: 0.77–0.99; P = 0.038) remained as independent risk factors for cardiac autonomic neuropathy in women.
Conclusions
A more atherogenic lipid profile such as the triglyceride: HDL cholesterol ratio and a smaller mean LDL cholesterol particle size were related to the prevalence of cardiac autonomic neuropathy in women with Type 2 diabetes.
Initial performance of the COSINE-100 experiment Adhikari, G.; Adhikari, P.; de Souza, E. Barbosa ...
The European physical journal. C, Particles and fields,
02/2018, Volume:
78, Issue:
2
Journal Article
Peer reviewed
Open access
COSINE is a dark matter search experiment based on an array of low background NaI(Tl) crystals located at the Yangyang underground laboratory. The assembly of COSINE-100 was completed in the summer ...of 2016 and the detector is currently collecting physics quality data aimed at reproducing the DAMA/LIBRA experiment that reported an annual modulation signal. Stable operation has been achieved and will continue for at least 2 years. Here, we describe the design of COSINE-100, including the shielding arrangement, the configuration of the NaI(Tl) crystal detection elements, the veto systems, and the associated operational systems, and we show the current performance of the experiment.
Cefazolin treatment failure has been observed in high-inoculum infections caused by methicillin-susceptible
Staphylococcus aureus
(MSSA) with a cefazolin inoculum effect (CIE). However, data on the ...characteristics and risk factors for the acquisition of CIE-positive MSSA infection are scarce. CIE positivity was measured as an MIC ≥ 16 μg/ml with a high inoculum (∼5 × 10
7
CFU/ml). The
blaZ
gene type was assessed through sequence analysis. The clinical characteristics and risk factors for the acquisition of CIE-positive MSSA infection were assessed. The association between the antimicrobial susceptibility profile and CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates showed a positive CIE; 254 (83.8 %) were positive for the
blaZ
gene. No significant association was found between CIE positivity and the site of infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10–7.48) and recent (≤1 month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76–12.50) were identified as significant risk factors for CIE-positive MSSA infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95 % CI, 1.62–7.80) and erythromycin (OR 5.00, 95 % CI, 2.50–9.99) were associated with CIE positivity, presenting high specificity (92.9 %) and a negative predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth of MSSA bacteraemia cases. Although CIE positivity was not clinically discernible, CIE positivity was associated with clindamycin or erythromycin susceptibility. Therefore, our findings suggest that cefazolin can be used in the treatment of high-inoculum MSSA infection if the isolates are susceptible to clindamycin or erythromycin.
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.
Background and purpose
Hemorrhagic transformation (HT) is one of the most problematic complications to arise from intravenous thrombolysis (IVT). This study was conducted to assess whether micro‐ and ...macroalbuminuria could be associated with HT after IVT in patients with acute ischaemic stroke, and to investigate whether the value of urinary albumin‐to‐creatinine ratios would correlate with the degree of HT.
Methods
This was a retrospective study of stroke patients who had undergone IVT within 3 h of symptom onset. Albuminuria assessment was based on random morning spot urine collection with patients in a fasting state, the first morning after IVT. Multiple logistic regression analysis was used to evaluate whether the presence of micro‐ and macroalbuminuria might be independent predictors of HT.
Results
One‐hundred and fifty‐four patients were included in the study. Fifty‐one patients had HT. The presence of micro‐ or macroalbuminuria was associated with HT after adjustment for variables with clinical significance (adjusting for age, atrial fibrillation, platelet counts, baseline National Institutes of Health Stroke Scale score, hypertension and diabetes mellitus; odds ratio, 2.542; 95% confidence interval, 1.106–5.841; P = 0.028). There were significant relationships between the presence of micro‐ and macroalbuminuria and types of HT.
Conclusion
In conclusion, the results of this study suggest that the presence of micro‐ and macroalbuminuria after IVT could be a predictor of severe HT in patients with acute ischaemic stroke.
Current microlensing surveys are sensitive to free-floating planets down to Earth-mass objects. All published microlensing events attributed to unbound planets were identified based on their short ...timescale (below two days), but lacked an angular Einstein radius measurement (and hence lacked a significant constraint on the lens mass). Here, we present the discovery of a Neptune-mass free-floating planet candidate in the ultrashort (tE = 0.320 0.003 days) microlensing event OGLE-2016-BLG-1540. The event exhibited strong finite-source effects, which allowed us to measure its angular Einstein radius of θE = 9.2 0.5 as. There remains, however, a degeneracy between the lens mass and distance. The combination of the source proper motion and source-lens relative proper motion measurements favors a Neptune-mass lens located in the Galactic disk. However, we cannot rule out that the lens is a Saturn-mass object belonging to the bulge population. We exclude stellar companions up to ∼15 au.
Summary
The incidence of atypical femoral fractures (AFFs) was 2.95% among 6644 hip and femoral fractures. Independent risk factors included the use of bisphosphonates (BPs), osteopenia or ...osteoporosis, rheumatoid arthritis, increased femoral curvatures, and thicker femoral cortices. Patients with AFFs and BP treatment were more likely to have problematic healing than those with typical femoral fractures (TFFs) and no BP treatment.
Introduction
To determine the incidence and risk factors of atypical femoral fractures (AFFs), we performed a multicenter case-control study. We also investigated the effects of bisphosphonates (BPs) on AFF healing.
Methods
We retrospectively reviewed the medical records and radiographs of 6644 hip and femoral fractures of patients from eight tertiary referral hospitals. All the radiographs were reviewed to distinguish AFFs from TFFs. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and interaction analyses were used to investigate the effects of BPs on fracture healing.
Results
The incidence of AFFs among 6644 hip and femoral fractures was 2.95% (90 subtrochanter and 106 femoral shaft fractures). All patients were females with a mean age of 72 years, and 75.5% were exposed to BPs for an average duration of 5.2 years (range, 1–17 years). The use of BPs was significantly associated with AFFs (
p
< 0.001, odds ratio = 25.65; 95% confidence interval = 10.74–61.28). Other independent risk factors for AFFs included osteopenia or osteoporosis, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex at the shaft level. Interaction analyses showed that patients with AFFs using BPs had a significantly higher risk of problematic fracture healing than those with TFFs and no BP treatment.
Conclusions
The incidence of AFFs among 6644 hip and femoral fractures was 2.95%. Osteopenia or osteoporosis, use of BPs, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex were independent risk factors for the development of AFFs. Patients with AFFs and BP treatment were more likely to have problematic fracture healing than those with TFFs and no BP treatment.
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