In this study, we undertook a randomized phase III trial of 105 NSCLC patients with oligo (one to four) -brain metastases. Patients were randomly assigned (1:1) to receive either stereotactic ...radiosurgery (SRS) followed by chemotherapy or upfront chemotherapy alone. The results demonstrated that SRS followed by chemotherapy did not improve overall survival compared with upfront chemotherapy only.
It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases.
We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome.
The median age was 58 years (range, 29–85) with ECOG 0–1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months 95% confidence interval (CI), 9.2–20.0 in the SRS group and 15.3 months (95% CI, 7.2–23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy),P = 0.248. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance.
Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients.
NCT01301560.
Background
Exposure to ambient air pollution and bronchiolitis are risk factors for asthma. The aim of this study was to investigate the effect of air pollution on the development of asthma in ...children with past episodes of bronchiolitis.
Methods
A prospective 2‐year follow‐up survey consisting of parental responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and allergy evaluations were conducted in 1743 children with a mean age of 6.8 years. Recent 5‐year exposure to air pollution was estimated using a geographic information system.
Results
Higher exposure to ozone was associated with airway hyper‐responsiveness (PC20 ≤ 16 mg/ml) at enrollment (odds ratio OR = 1.60, 95% CI confidence interval = 1.13–2.27) and with new episodes of wheezing during the 2‐year period (OR = 1.92, 95% CI = 0.96–3.83). Past episodes of bronchiolitis were associated with both current wheezing and physician‐diagnosed asthma. When the two factors were combined, the prevalence of bronchial hyper‐reactivity (OR = 2.96, 95% CI = 1.41–6.24) and new wheezing (OR = 4.17, 95% CI = 0.89–19.66) as well as current wheezing and physician‐diagnosed asthma was even greater (P for trend <0.05 for all). In children with both risk factors, lung function was significantly decreased, with atopic children being particularly vulnerable.
Conclusion
In children, the interaction between air pollution and past episodes of bronchiolitis resulted in a greater prevalence of asthma and pointed to an association with bronchial hyper‐reactivity and decreased lung function. These results suggest mechanisms underlying the development of asthma.
Background
Recurrence of pancreatic cancer after primary pancreatectomy occurs in the vast majority of patients. The role of surgical treatment for recurrent pancreatic cancer is not well ...established.
Methods
Patients who underwent primary pancreatectomy with curative intent from 2000 to 2014 at a single large‐volume centre were evaluated retrospectively. CT or PET was used to select patients with an isolated recurrence. The clinicopathological features and survival outcomes were compared according to treatment modalities.
Results
Of the 1610 patients with pancreatic cancer who underwent resection, 1346 (83·6 per cent) were diagnosed with recurrent pancreatic cancer. Recurrence was locoregional in 366 patients (27·2 per cent), distant multifocal in 251 (18·6 per cent), distant isolated in 188 (14·0 per cent), locoregional plus distant in 153 (11·4 per cent) and peritoneal seeding in 388 (28·8 per cent). Of the 1346 patients with recurrence, 197 (14·6 per cent) had isolated recurrence; of these, 48 (24·4 per cent of all isolated recurrences; 3·6 per cent of all recurrences) underwent resection. Median survival of the 197 patients after diagnosis of isolated recurrence was 14·7 months; it was longer in patients who underwent surgical resection than among those treated non‐surgically (23·5 versus 12·0 months; P = 0·014). Multivariable analysis showed that chemotherapy and resection for recurrence were associated with better prognosis. Median survival after recurrence was longest in the 23 patients with isolated pulmonary recurrence (33·3 months). Survival after recurrence was better in patients who underwent resection of isolated recurrence in the remnant pancreas (median 28·0 versus 12·0 months, P = 0·010) and lung (median 36·5 versus 9·5 months; P = 0·010) than in those who did not undergo resection.
Conclusion
Surgical resection may be considered an option for treatment of patients with isolated recurrent pancreatic cancer.
For the select few
Summary
The wide geographic spread of Eurasian Goose/Guangdong lineage highly pathogenic avian influenza (HPAI) clade 2.3.4.4 viruses by wild birds is of great concern. In December 2014, an H5N8 HPAI ...clade 2.3.4.4 Group A (2.3.4.4A) virus was introduced to North America. Long‐distance migratory wild aquatic birds between East Asia and North America, such as Northern Pintail (Anas acuta), were strongly suspected of being a source of intercontinental transmission. In this study, we evaluated the pathogenicity, infectivity and transmissibility of an H5N8 HPAI clade 2.3.4.4A virus in Northern Pintails and compared the results to that of an H5N1 HPAI clade 2.3.2.1 virus. All of Northern Pintails infected with either H5N1 or H5N8 virus lacked clinical signs and mortality, but the H5N8 clade 2.3.4.4 virus was more efficient at replicating within and transmitting between Northern Pintails than the H5N1 clade 2.3.2.1 virus. The H5N8‐infected birds shed high titre of viruses from oropharynx and cloaca, which in the field supported virus transmission and spread. This study highlights the role of wild waterfowl in the intercontinental spread of some HPAI viruses. Migratory aquatic birds should be carefully monitored for the early detection of H5 clade 2.3.4.4 and other HPAI viruses.
Summary
We evaluated the correlation between central bone mineral density (BMD) and peripheral bone attenuation using lower extremity computed tomography (CT). A good correlation was found between ...lower extremity CT and central BMD suggesting that CT is useful for screening osteoporosis, and that peripheral bone attenuation adequately reflects central BMD.
Introduction
This study aimed to evaluate the reliability and validity of CT as a screening tool for osteoporosis and to estimate the correlation between central BMD and peripheral bone attenuation using lower extremity CT.
Methods
In total, 292 patients who underwent a lower extremity, lumbar spine, or abdomen and pelvic CT scan within a 3-month interval of a dual-energy X-ray absorptiometry (DEXA) examination were included. Following reliability testing, bone attenuation of the L1, L2, L3, L4, femoral head, femoral neck, greater trochanter, distal femur, proximal tibia, distal tibia, and talus was measured by placing a circular region of interest on the central part of each bony region on a coronal CT image. Partial correlation was used to assess the correlation between CT and DEXA after adjusting for age and body mass index.
Results
In terms of reliability, all bone attenuation measurements, except the femoral neck, showed good to excellent interobserver reliability (intraclass correlation coefficients, 0.691–0.941). In terms of validity, bone attenuation of the L1 to L4, femoral neck, and greater trochanter on CT showed significant correlations with BMD of each area on DEXA (correlation coefficients, 0.399–0.613). Bone attenuation of the distal tibia and talus on CT showed significant correlations with BMD of all parts on DEXA (correlation coefficients, 0.493–0.581 for distal tibia, 0.396–0.579 for talus).
Conclusion
Lower extremity CT is a useful screening tool for osteoporosis, and peripheral bone attenuation on lower extremity CT adequately reflects central BMD on DEXA.
Bronchoalveolar lavage (BAL) and bronchial washing (BW) are two major methods used to obtain high-quality respiratory specimens from patients with suspected pulmonary tuberculosis (TB) but a ...sputum-scarce or smear-negative status. We aimed to compare the value of BAL and BW in the diagnosis of TB in such patients.
We enrolled patients with suspected pulmonary TB but with a sputum-scarce or smear-negative status who were referred for bronchoscopy between October 2013 and January 2016. Participants were randomized into the BAL and BW groups for evaluation. The primary outcome was the diagnostic yield for TB detection. Secondary outcomes included culture positivity, positivity of nucleic acid amplification tests (NAATs) for Mycobacterium tuberculosis and procedure-related complications.
A total of 94 patients were assessed and 91 (43 in the BAL group, 48 in the BW group) were analysed. Twenty-one patients (48.8%) in the BAL group and 30 (62.5%) in the BW group had a final diagnosis of pulmonary TB. The detection rate of M. tuberculosis by culture or NAAT was significantly higher in BAL specimens than in BW specimens (85.7% vs 50.0%, p 0.009). The procedure-related complications were hypoxic events, 2/43 (4.7%) in the BAL group and 5/48 (10.4%) in the BW group; and post-bronchoscopic fever, 3/43 (7.0%) in the BAL group and 4/48 (8.3%) in the BW group.
As long as it is tolerable, BAL rather than BW, should be used to obtain specimens for the diagnosis of pulmonary TB in sputum-scarce or smear-negative cases.
Vapor‐phase polymerization is used for the first time to prepare ultrathin, polycrystalline conducting films of poly(3,4‐ethylenedioxythiophene) (PEDOT). The polarized optical microscopy images (see ...figure) display the progress of crystalline growth at 30 °C: a) initial step of self‐assembled PEDOT film formation (amorphous shape); b) nucleation; c) crystalline growth; and d) dendritic growth. The scale is 100 × 100 μm2.
Aims: Research is to identify the bioactive secondary metabolites produced by Aspergillus sp. KMD 901 isolated from marine sediment and to assess their apoptosis‐inducing effects. Methods and ...Results: Aspergillus sp. KMD 901 was isolated from marine sediment obtained from the East Sea of Korea. An ethyl acetate extract of KMD 901 exhibited potent cytotoxic activity towards five cancer cell lines (HCT116, AGS, A549, MCF‐7 and HepG2). Sequencing of the internal transcribed spacer (ITS) region in this strain allowed us to identify KMD 901 as a strain of Aspergillus versicolor. The cytotoxic compounds from Aspergillus sp. KMD 901 were purified by reversed‐phase high‐performance liquid chromatography and identified as diketopiperazine disulfides through spectroscopic analyses including extensive 2D NMR and mass spectrometry. The diketopiperazine disulfides were found to induce apoptosis in HCT116 cells based on cell morphology, DNA fragmentation observed by agarose gel electrophoresis, Annexin‐V/PI staining using a flow cytometer and cleavage of poly (ADP‐ribose) polymerase (PARP), caspase‐3, caspase‐8, caspase‐9 and Bcl‐2 family proteins (Bcl‐2, Bcl‐xL and Bax) using Western blotting analysis. Further study using an in vivo xenograft model showed inhibitory effects of acetylapoaranotin (2) on tumour proliferation. Conclusion: A new diketopiperazine disulfide, deoxyapoaranotin (3), along with previously described acetylaranotin (1) and acetylapoaranotin (2) was separated from Aspergillus sp. KMD 901 and found to have direct cytotoxic and apoptosis‐inducing effects towards HCT116 colon cancer cell lines. Significance and Impact of the Study: These results suggest that the diketopiperazine disulfides produced from Aspergillus sp., KMD 901, could be candidates for the development of apoptosis‐inducing antitumour agents. Also, this study indicates that marine natural products as potential source of pharmaceuticals.
The aims of this study were to determine if the chicken embryo lethality assay and the presence of 9 virulence-associated genes of Escherichia coli were correlated and to discover which virulence ...genes contributed most to embryo lethality. We examined 58 E. coli strains isolated from visceral organs of chickens with colibacillosis for the presence of 9 virulence genes (fimC, tsh, fyuA, irp2, iucD, cvi/cva, iss, astA, and vat) by PCR. The gene FimC (type I fimbriae) was detected with the highest prevalence in 93.1% of the isolates, followed by iucD (67.24%), iss (58.62%), tsh (34.48%), cvi/cva (34.48%), fyuA (32.76%), astA (31.0%), irp2 (27.59%), and vat (17.24%). The embryo mortality ranged from 5 to 100%; however, most of the isolates were moderately or highly virulent. High positive correlations were observed between the presence of virulence genes and chicken embryo lethality. In addition, presence of the iucD (aerobactin) gene was the trait that best contributed to embryo mortality by using the multivariate model. These results suggest that expression frequency of these 9 virulence genes is associated with embryo mortality, and the gene that best predicted embryo mortality was iucD.
The purpose of diet-quality indices is to assess and guide individual dietary intake for the promotion of health and prevention of disease, and food based dietary-quality indices need to be applied ...by using each country's own unique diet. We assessed the relationships between relatively simple dietary quality scores modified for a Korean diet, such as the Recommended Food Score (RFS) and alternate Mediterranean Diet Score (aMDS), and oxidative stress biomarkers in Korean adults.
A total of 976 adults were recruited for the Biomarker Monitoring for Environmental Health Study between April and December 2005 in Seoul and Incheon, Korea. RFS and aMDS were calculated by using a food-frequency questionnaire. We used regression analyses to assess the associations between diet quality scores and urinary malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG).
RFS and aMDS were negatively associated with urinary MDA concentrations (P=0.032 for RFS, P=0.043 for aMDS), but not with 8-OHdG after adjusted for potential covariates. After stratified analyses by sex, negative associations between the both scores and urinary MDA concentrations were not significant in both men and women. There were no significant associations of RFS and aMDS with urinary 8-OHdG concentrations.
Higher RFS and aMDS scores were related to lower oxidative stress. Therefore, good quality of diet may be useful in reducing oxidative stress.
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