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.
Although capsule endoscopy has become a central diagnostic tool for small-bowel evaluation, retention of a capsule remains a major concern. This study attempted to investigate the incidence and ...clinical outcomes of capsule retention, and to determine the factors predictive of spontaneous capsule passage after retention.
Through a nationwide multicenter survey, we retrospectively reviewed the records of 1291 patients who had a capsule endoscopy between February 2002 and July 2006 in Korea. Clinical and procedural characteristics and postprocedural outcomes were analyzed for the cases with capsule retention.
Capsule retention occurred in 2.5 % of total cases (32/1291). The major diseases accompanying capsule retention were Crohn's disease, malignant tumors, and tuberculous enterocolitis, in decreasing order. In 11 of the 32 patients (34.4 %), early surgical or endoscopic interventions were instituted for diagnosis or treatment of diseases before retention symptoms developed. The remaining 21 (65.6 %) patients initially received medical treatments. Of these, 10 (31.3 %) ultimately underwent surgical intervention due to the development of symptoms of intestinal obstruction or medical treatment failure. The other 11 (34.4 %) eventually passed the capsule. The presence of a larger lumen diameter (greater than two-thirds of the capsule diameter) at the stricture site was associated with spontaneous passage.
Our large-scale study suggests that retention occurs infrequently during capsule endoscopy. Moreover, a retained capsule might indicate the best intervention for the offending pathology, or it may spontaneously pass in the long run, particularly in patients with less small bowel stricture.
Rectal carcinoids are low-grade malignancies that are usually treated by endoscopic resection. However, on pathologic examination, resection margins that are positive for carcinoid cells are ...frequently found. Patient outcomes were reviewed after endoscopic resection of rectal carcinoids and the clinical significance of possible residual disease, as defined by pathologic and endoscopic examination, was evaluated.
The medical records and endoscopic findings of 347 patients presenting with rectal carcinoids to 14 university hospitals in Korea between January 1999 and June 2007 were retrospectively analyzed.
A total of 304 patients were treated with endoscopic resection, and 43 patents were treated with surgery. In the endoscopic resection group, the complete resection rate was 88.2% based on endoscopic appearance (CR-E) and 60.2% based on pathologic evaluation (CR-P). The agreement between CR-E and CR-P was low (κ=0.192). No residual tumors were found in 77 of 85 patients (90.6%) who were CR-E but not CR-P and who had endoscopic biopsy taken at 24-month follow-up. The receiver-operating characteristic curve identified an optimal cut-off value of 10.5 mm, at which the sensitivity and the specificity for metastasis were 100% and 89%, respectively. The risk factors for metastasis by multivariate analysis were tumor size, increased mitotic rate, and lymphovascular invasion.
Endoscopic resection is a safe and effective modality for treating well-differentiated rectal carcinoids smaller than 10 mm in diameter. Discrepancies were observed between CR-E and CR-P. The risk factors for metastasis were tumor size, increased mitotic rate, and lymphovascular invasion.
Background and purpose
The objective of this study was to investigate the association between body mass index (BMI) and both initial stroke severity at presentation and functional outcomes after ...acute ischaemic stroke (AIS) in patients with non‐valvular atrial fibrillation (NVAF).
Methods
Patients were categorized on the basis of their BMI into underweight (BMI <18.5, n = 111), normal (18.5 ≤ BMI <25, n = 1036) and overweight to obese (BMI ≥25, n = 472) groups. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score and functional outcomes were assessed using the modified Rankin Scale score at discharge. The differences in stroke severity and functional outcomes were compared between groups using robust log‐linear regression with a Poisson distribution and binary logistic regression analysis.
Results
A total of 1619 AIS patients with NVAF from six hospitals were included. Compared with the NIHSS scores median 5, interquartile range (IQR) 2–14 of normal‐weight patients, the NIHSS scores (median 9, IQR 4–19) of underweight patients were more likely to be higher, whereas those of overweight to obese patients were lower (median 4, IQR 1–12) (P < 0.001). In terms of functional outcomes after stroke, underweight patients had a higher risk of poor functional outcomes (odds ratio 1.78, 95% confidence interval 1.09–2.56, P = 0.01) but overweight to obese patients had no significant difference in functional outcomes compared with normal‐weight patients.
Conclusion
An inverse association was found between BMI and stroke severity in AIS patients with NVAF. This suggests the presence of an obesity paradox for short‐term outcomes in patients with NVAF.
In this review, we describe dielectric properties of biological tissues and liquids in the context of terahertz (THz) biophotonics. We discuss a model of the THz dielectric permittivity of water and ...water-containing media, which yields analysis of the relaxation and damped resonant molecules modes. We briefly describe modern techniques of THz spectroscopy and imaging employed in biophotonics with a strong emphasize on a THz time-domain spectroscopy. Furthermore, we consider the methods of sub-wavelength resolution THz imaging and the problem of THz wave delivery to hard to access tissues and internal organs. We consider the THz dielectric properties of biological solutions and liquids. Although strong absorption by water molecules prevents THz-waves from penetration of hydrated tissues and probing biological molecules in aqueous solutions, we discuss approaches for overcoming these drawbacks – novel techniques of freezing and temporal dehydration by application of hyperosmotic agents which have a potential for cancer detection. We review recent applications of THz technology in diagnosis of malignancies and aiding histology paying particular attention to the origin of contrast observed between healthy and pathological tissues. We consider recent applications of THz reflectometry in sensing the thinning dynamics of human pre-corneal tear film. Modern modalities of THz imaging, which relies on the concepts of multi-spectral and multi-temporal domains and employing the principles of color vision, phase analysis and tomography are discussed. Novel methods of THz spectra analysis based on machine learning, pattern recognition, chemical imaging and the revealing of the spatial distribution of various substances in a tissue, are analyzed. Advanced thermal model describing biological object irradiated by THz waves and phantoms mimicking the optical properties of tissues at THz frequencies are presented. Finally, application of the high-resolution THz spectroscopy in analytic chemistry, biology and medicine are described.
Using the entire Belle data sample of 980 fb−1 of e+e− collisions, we present the results of a study of excited Ωc charmed baryons in the decay mode Ξc+K−. We show confirmation of four of the five ...narrow states reported by the LHCb Collaboration: the Ωc(3000), Ωc(3050), Ωc(3066), and Ωc(3090).
Poly(3-hexylthiophene) (P3HT) is combined with a series of C
60
-based derivatives with LUMO energies varying between −3.53 and −3.83 eV, in order to study the influence of the fullerene LUMO level ...on the performance and stability of organic solar cells as well as the degradation of the photoactive materials. UV/vis measurements show that P3HT degrades more slowly in all investigated P3HT:fullerene blends compared to neat P3HT films when being irradiated in air. Accordingly, all fullerene derivatives stabilize P3HT against photo-oxidation, albeit to different extents, with the electron affinity of the fullerene determining the degree of stabilization. A fullerene LUMO level of −3.75 eV is found to cause maximum stabilization, while the degradation rate increases for higher and lower values. Remarkably, the higher the stabilization effect imposed by the fullerene the slower the fullerene degrades itself, which indicates a non-sacrificial mode of stabilization. Transient absorption spectroscopy measurements show similar kinetics of exciton quenching and charge generation for all P3HT:fullerene combinations indicating a similar morphology in all blend films. Inverted solar cells made from the different P3HT:fullerene blends exhibit a good correlation between fullerene LUMO level and open-circuit voltage. Upon illumination in air, the photovoltaic devices follow the same degradation trend as the isolated photoactive layers by showing the same dependence on the fullerene LUMO level. Finally, we discuss different mechanisms, by which fullerene acceptors are potentially able to stabilize (UV light screening, excited-state quenching, and radical scavenging) as well as destabilize (morphological effects, superoxide or singlet oxygen sensitization, and polymer triplet-state population) donor polymers.
The photo-oxidation rates of seven different P3HT:fullerene films and solar cells are correlated with the electron affinities of the fullerene derivatives. The potential (de)stabilizing mechanisms imposed by the fullerenes are discussed and assessed.
We report here measurement of the cross section of e+e- → π+π-ψ ( 2S ) between 4.0 and 5.5 GeV, based on an analysis of initial state radiation events in a 980fb-1 data sample recorded with the Belle ...detector. The properties of the Y ( 4360 ) and Y ( 4660 ) states are determined. Fitting the mass spectrum of π+π-ψ ( 2S ) with two coherent Breit-Wigner functions, we discover two solutions with identical mass and width but different couplings to electron-positron pairs: MY ( 4360 ) = ( 4347±6±3 ) MeV / c2 , Γ Y ( 4360 ) = ( 103±9±5 ) MeV , MY ( 4660 ) = ( 4652±10±8 ) MeV / c2 , Γ Y ( 4660 ) = ( 68±11±1 ) MeV ; and B Y ( 4360 ) → π+π-ψ ( 2S ) · Γ Y ( 4360 ) e+e-= ( 10.9±0.6±0.7 ) eV and B Y ( 4660 ) → π+π-ψ ( 2S ) · Γ Y ( 4660 ) e+e-= ( 8.1±1.1±0.5 ) eV for one solution; or B Y ( 4360 ) → π+π-ψ ( 2S ) · Γ Y ( 4360 ) e+e-= ( 9.2±0.6±0.6 ) eV and B Y ( 4660 ) → π+π=ψ ( 2S ) · Γ Y ( 4660 ) e+e-= ( 2.0±0.3±0.2 ) eV for the other. Here, the first errors are statistical and the second systematic. Evidence for a charged charmoniumlike structure at 4.05GeV / c2 is observed in the π±ψ ( 2S ) intermediate state in the Y ( 4360 ) decays. decays.
The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been ...discussed as a novel and effective method for decolonizing MDRO.
To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage.
This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube.
A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P = 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P = 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio = 6.810, P = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT.
Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.
The aim of this study was to determine the hydraulic pressures necessary to separate and lift the sinus membrane from the sinus floor in order to ensure a more controlled and safer hydraulic ...transcrestal sinus lifting surgery and prevent sinus membrane perforation. A flow-regulating hydrodynamic device with a pressure sensor was used in nine patients. The hydraulic pressure was found to increase steadily up to a mean peak of 25.0±13.0kPa, which is comparable to the medium suction power of ordinary vacuum cleaners. Subsequently, there was a short plateau followed by a sharp decrease in the hydraulic pressure.
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