CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor ...(EGFR).
Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m2) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data.
From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40–0.75, P < 0.001 as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38–0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49–1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43–2.08, P = 0.877).
CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients.
NCT00891579.
Background
Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)‐HVTT ...model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection.
Methods
Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH‐HVTT model with contour plot was developed using a non‐linear model in the training cohort, and subsequently validated in internal and external cohorts.
Results
Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH‐HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low‐ and high‐risk groups with distinct long‐term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus.
Conclusion
The EHBH‐HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.
Antecedentes
La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)‐HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes.
Métodos
Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH‐HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas.
Resultados
De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH‐HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P < 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente.
Conclusión
El modelo EHBH‐HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.
The Eastern Hepatobiliary Surgery Hospital–hepatic vein tumour thrombus (EHBH‐HVTT) model was accurate in predicting prognosis in patients with hepatocellular carcinoma (HCC) and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including inferior vena cava tumour thrombus, or coexisting portal vein tumour thrombus (PVTT).
predicts prognosis
To confront energy shortage, global warming and climate changes, biofuels derived from biomass have received increasing attention from the industry, academia and governments. Of the potential sources ...of biofuels a most promising one is the simple photosynthetic microalgae, which can be grown in open ponds, photobioreactors and fermenters. The advantages to produce biofuels from microalgae include easy adaption to environmental conditions, high photosynthesis efficiency, high lipid content and noncompetition for farmlands. Nonetheless, the real hallmark of microalgae is the fact that these microscopic organisms can provide the biomass feedstock for the flexible production of several different types of renewable and sustainable biofuels such as biodiesel, bioethanol, biogas, biohydrogen among others via thermochemical and biochemical conversion processes. Amazingly, from a sustainability perspective the integrated algal biofuels production, where biodiesel, bioethanol and biogas are continuously produced from one biomass source, can evidently lead to an increase in the energetic productivity of the microalgal biomass, thus improving the economics of this algal biorefinery approach. Developments in several areas, such as genetic and metabolic engineering, are expected to further improve the costeffectiveness of the biofuels from microalgae in an environmentally sustainable manner.
Objective and design
Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether ...dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury.
Materials
Acute kidney injury in mice was induced by cisplatin.
Treatments
Mice were administered with DEX 25 μg/kg or atipamezole 250 μg/kg (once a day, for 3 days) after cisplatin treatment.
Methods
The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80
+
macrophages, CD3
+
T cells, and NF-κB were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction.
Results
DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-κB activation and decreased expression of TNF-α, IL-1β, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to α
2
adrenoceptor-dependent pathway.
Conclusion
We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response.
An epidemic of severe acute respiratory syndrome (SARS) has been associated with an outbreak of atypical pneumonia originating in Guangdong Province, People's Republic of China. We aimed to identify ...the causative agent in the Guangdong outbreak and describe the emergence and spread of the disease within the province.
We analysed epidemiological information and collected serum and nasopharyngeal aspirates from patients with SARS in Guangdong in mid-February, 2003. We did virus isolation, serological tests, and molecular assays to identify the causative agent.
SARS had been circulating in other cities of Guangdong Province for about 2 months before causing a major outbreak in Guangzhou, the province's capital. A novel coronavirus, SARS coronavirus (CoV), was isolated from specimens from three patients with SARS. Viral antigens were also directly detected in nasopharyngeal aspirates from these patients. 48 of 55 (87%) patients had antibodies to SARS CoV in their convalescent sera. Genetic analysis showed that the SARS CoV isolates from Guangzhou shared the same origin with those in other countries, and had a phylogenetic pathway that matched the spread of SARS to the other parts of the world.
SARS CoV is the infectious agent responsible for the epidemic outbreak of SARS in Guangdong. The virus isolated from patients in Guangdong is the prototype of the SARS CoV in other regions and countries.
The molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method is constantly used to calculate the binding free energy of protein-ligand complexes, and has been shown to effectively balance ...computational cost against accuracy. The relative binding affinities obtained by the MM/PBSA approach are acceptable, while it usually overestimates the absolute binding free energy. This paper proposes four free energy estimators based on the MM/PBSA for enthalpy change combined with interaction entropy (IE) for entropy change using different weights for individual energy terms. The ΔG
method is determined to be an optimal estimator based on its performance in terms of the correlation between experimental and theoretical values and error estimations. This approach is optimized using high-quality experimental values from a training set containing 84 protein-ligand systems, and the coefficients for the sum of electrostatic energy and polar solvation free energy, van der Waals (vdW) energy, non-polar solvation energy and entropy change are obtained by multivariate linear fitting to the corresponding experimental values. A comparison between the traditional MM/PBSA method and this method shows that the correlation coefficient is improved from 0.46 to 0.72 and the slope of the regression line increases from 0.10 to 1.00. More importantly, the mean absolute error (MAE) is significantly reduced from 22.52 to 1.59 kcal mol
. Furthermore, the numerical stability of this method is validated on a test set with a similar correlation coefficient, slope and MAE to those of the training set. Based on the above advantages, the ΔG
method can be a powerful tool for a reliable and accurate estimation of binding free energy and plays a significant role in a detailed energetic investigation of protein-ligand interaction.
Free-electron lasers have been successfully operated with ultrahigh brightness and excellent transverse coherence at X-ray wavelengths. One of the next goals for further improvements is full ...coherence. An obvious approach is to seed the free-electron laser interaction using a conventional source that has good temporal coherence. Here, we show the first lasing of a free-electron laser with an echo-enabled harmonic generation scheme, which shows great promise for producing coherent lasing at short wavelengths, even in the X-ray regime. The experiment was conducted at a test facility that combines a 135.4 MeV electron accelerator with an amplifier consisting of a series of undulator magnets. Lasing was achieved at the third harmonic of the seed with a gain of ∼100,000 over spontaneous radiation. The measurements show typical exponential growth and excellent spectral characteristics, as well as good intensity stability.
When face-centered cubic (FCC) metals and alloys with low stacking fault energy (SFE) are irradiated by high-energy particles or deformed at high speed, stacking fault tetrahedra (SFTs), which are a ...type of vacancy cluster defect, are often formed. Therefore, SFTs were expected to form in the CoCrFeMnNi equiatomic high-entropy alloy (HEA). However, no SFT was observed in the CoCrFeMnNi HEA with high-speed plastic deformation even after annealing at 873 K. To elucidate this mechanism, the binding energy of vacancy clusters in the CoCrFeMnNi HEA was calculated based on first principles. The binding energy of the di-vacancy cluster was positive (average of 0.25 eV), while that of the tri-vacancy cluster was negative (average of - 0.44 eV), suggesting that the possibility of formation of a tri-vacancy cluster was low. The inability to form a cluster containing three vacancies is attributed to the excellent irradiation resistance of the CoCrFeMnNi HEA. However, if an extra vacancy is added to a tri-vacancy cluster (with negative binding energy), the binding energy of the subsequent tetra-vacancy cluster may become positive. This suggests that it is possible to form vacancy clusters in the CoCrFeMnNi HEA when high-energy ion or neutron irradiation causes cascade damage.
Objectives
The impact of electrolyte imbalance on clinical outcomes after acute ischemic stroke (AIS) is still not understood. We investigated the association between hypochloremia and hyponatremia ...upon hospital admission and in‐hospital mortality in AIS patients.
Materials and methods
A total of 3314 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in this study. Hypochloremia was defined as having a serum chloride concentration <98 mmol/L and hyponatremia as having a serum sodium concentration <135 mmol/L. The Cox proportional hazard model was used to examine the effect of hypochloremia and hyponatremia on all‐cause in‐hospital mortality in AIS patients.
Results
During hospitalization, 118 patients (3.6%) died from all causes. Multivariable model adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, serum sodium, and other potential covariates showed that hypochloremia was associated with a 2.43‐fold increase in the risk of in‐hospital mortality (hazard ratio HR 2.43; 95% confidence interval CI, 1.41‐4.19; P=.001). However, no significant association between hyponatremia (P=.905) and in‐hospital mortality was observed. Moreover, the multivariable analysis found that serum chloride (HR=0.92, 95% CI 0.88‐0.98; P=.004) but not serum sodium (P=.102) was significantly associated with in‐hospital mortality.
Conclusions
Hypochloremia at admission was independently associated with in‐hospital mortality in AIS patients.
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