Summary
Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent ...significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs).
Introduction
Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs.
Methods
A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups group I (
n
= 39, no anti-osteoporosis medication), group II (
n
= 66, bisphosphonate), and group III (
n
= 27, parathyroid hormone (PTH). Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type.
Results
IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5,
p
< 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325).
Conclusions
Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.
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.
Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism’s ...pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.
Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the ...prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.
Quasi‐biennial oscillations (QBOs) in thirteen atmospheric general circulation models forced with both observed and annually repeating sea surface temperatures (SSTs) are evaluated. In most models ...the QBO period is close to, but shorter than, the observed period of 28 months. Amplitudes are within ±20% of the observed QBO amplitude at 10 hPa, but typically about half of that observed at lower altitudes (50 and 70 hPa). For almost all models, the oscillation's amplitude profile shows an overall upward shift compared to reanalysis and its meridional extent is too narrow. Asymmetry in the duration of eastward and westward phases is reasonably well captured, though not all models replicate the observed slowing of the descending westward shear. Westward phases are generally too weak, and most models have an eastward time mean wind bias throughout the depth of the QBO. The intercycle period variability is realistic and in some models is enhanced in the experiment with observed SSTs compared to the experiment with repeated annual cycle SSTs. Mean periods are also sensitive to this difference between SSTs, but only when parametrized non‐orographic gravity wave (NOGW) sources are coupled to tropospheric parameters and not prescribed with a fixed value. Overall, however, modelled QBOs are very similar whether or not the prescribed SSTs vary interannually. A portrait of the overall ensemble performance is provided by a normalized grading of QBO metrics. To simulate a QBO, all but one model used parametrized NOGWs, which provided the majority of the total wave forcing at altitudes above 70 hPa in most models. Hence the representation of NOGWs either explicitly or through parametrization is still a major uncertainty underlying QBO simulation in these present‐day experiments.
Quasi‐biennial oscillations (QBOs) in thirteen atmospheric general circulation models forced with both observed (orange) and annually repeating (grey) sea surface temperatures (SSTs) are evaluated over a range of metrics and compared against reanalysis (blue‐green). Mean periods are sensitive to this difference between SSTs, but only when parametrized non‐orographic gravity wave sources are coupled to tropospheric parameters (60LCAM5 and right there of) and not prescribed with fixed values. Overall, however, modelled QBOs are very similar whether or not the prescribed SSTs vary interannually.
Multicentre study.
To define the clinical characteristics of patients with tuberculosis (TB) destroyed lung due to past TB.
We reviewed patients with TB-destroyed lung between May 2005 and June 2011.
...A total of 595 patients from 21 hospitals were enrolled. The mean age was 65.63 ± 0.47 (mean ± standard error); 60.5% were male. The mean number of lobes involved was 2.59 ± 0.05. Pleural thickening was observed in 54.1% of the patients. Mean forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC, bronchodilator response and number of exacerbations per year were respectively 2.06 ± 0.03 l (61.26% ± 0.79), 1.16 ± 0.02 l (49.05% ± 0.84), 58.03% ± 0.70, 5.70% ± 0.34, and 0.40 ± 0.04. The number of lobes involved was significantly correlated with FVC and FEV(1), and with the number of exacerbations per year. Use of long-acting muscarinic antagonists or long-acting beta-2 agonists plus inhaled corticosteroids resulted in bronchodilatory effects. Multivariable regression analysis showed that age, initial FEV(1) (%) and number of exacerbations during follow-up were independent factors affecting change in FEV(1).
Decreased lung function with exacerbation, and progressive decline of FEV(1) were observed in patients with TB-destroyed lung.
Summary
Incidence of hip fracture increased in Korean populations over age 50 between 2008 and 2012, and the number of fractures was predicted to increase by 1.4 times by 2025. This is important ...information for public health planning.
Introduction
The purposes of this study were to evaluate the trends in the incidence and mortality of hip fracture between 2008 and 2012 and predict the number of hip fractures in Korea through 2025 using nationwide claims data.
Methods
The data managed by the National Health Insurance Service were used to identify the hip fractures in patients aged >50 years between 2008 and 2012. Projections of hip fractures were conducted using the Poisson distribution from 2016 to 2025 in Korea.
Results
The incidence of hip fractures (per 100,000) increased by 14.1 % over the 5 years of the study, by 15.8 % in women and 10.9 % in men; the older age group showed a steep rise and shift in the incidence from 2008 to 2012. The cumulative mortality rates at 1 year after hip fractures were 17.2 % (3575/20,849) in 2008 and 16.0 % (4547/28,426) in 2012. Overall standardized mortality ratios (SMRs) for hip fracture were higher in men (11.93) than in women (11.22) and were higher than those in the general population in all age groups. In 2016, the total number of hip fractures was estimated to increase an overall of 1.4 times by 2025.
Conclusions
The incidence of hip fracture continues to increase, and the related mortality is still high, although it has decreased over time. The socioeconomic burden of hip fracture is expected to increase in Korea along with the increased estimated number of fractures. Nationwide strategies should include attempts to reduce the future socioeconomic burdens of hip fractures.
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.
We present microlensing events in the 2015 Korea Microlensing Telescope Network (KMTNet) data and our procedure for identifying these events. In particular, candidates were detected with a novel ..."completed-event" microlensing event-finder algorithm. The algorithm works by making linear fits to a grid of point-lens microlensing models. This approach is rendered computationally efficient by restricting u0 to just two values (0 and 1), which we show is quite adequate. The implementation presented here is specifically tailored to the commission-year character of the 2015 data, but the algorithm is quite general and has already been applied to a completely different (non-KMTNet) data set. We outline expected improvements for 2016 and future KMTNet data. The light curves of the 660 "clear microlensing" and 182 "possible microlensing" events that were found in 2015 are presented along with our policy for their public release.
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a ...possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1
; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca
/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1
; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
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