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
The Child–Pugh (CP) score is used widely to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the albumin–bilirubin (ALBI) ...score has been validated as a predictor of overall survival in these patients. This study aimed to compare the ability of the ALBI and CP scores to predict outcomes in patients with HCC after liver resection with curative intent.
Methods
Consecutive patients who underwent liver resection with curative intent for HCC between January 2007 and July 2013 were included in this retrospective study. The performance of the ALBI score in predicting postoperative liver failure (PHLF) and long‐term survival was compared with that of the CP score.
Results
A total of 1242 patients were enrolled. Of these, 166 (13·4 per cent) experienced PHLF. The area under the receiver operating characteristic (ROC) curve of the ALBI score for predicting PHLF was greater than that of the CP score (0·723 versus 0·607; P < 0·001). Similar to findings for CP grade, the incidence and severity of PHLF increased with increasing ALBI grade. The ALBI grade stratified patients into at least two distinct overall survival cohorts (P < 0·001), whereas the CP grade did not. The ALBI grade also classified patients with CP grade A disease into two distinct overall survival cohorts (P < 0·001), and overall survival rates in the group with poorer survival were similar to those in the majority of patients with CP grade B disease. Both CP and ALBI scores had low power in predicting disease‐free survival.
Conclusion
The ALBI grade predicted PHLF and overall survival in patients with HCC undergoing liver resection with curative intent more accurately than the CP grade.
ALBI score may be better
Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the ...purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.
A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P<0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P=0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.
In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and ...neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.
It is well‐known that ground‐level ozone is not just a local or regional air quality problem; emission sources from super‐regional (sources outside the PRD region) scales are known to contribute ...significantly to local ozone concentrations. However, source apportionment studies differentiating the relative contributions of local, regional, and super‐regional ozone precursors are still limited. In this paper, using the Pearl River Delta (PRD) as an example, we have conducted a detailed apportionment (by source categories and by source regions) study of surface ozone using photochemical model source apportionment tools. Our results show that, while the super‐regional contribution is dominant under mean ozone conditions, elevated local and regional sources are the causative factor for the formation of high ozone episodes. In particular, the local and PRD regional contributions increase from about 30% during non‐episode days to about 50% during high ozone episode days in the autumn (November 2006) and even up to about 70% during high ozone episodes in the summer (July 2006). These results suggest that local and regional controls of ozone precursors are still very important for ozone reduction, particularly for episodic events. Furthermore, our results show that mobile emission is by far the highest contributing source category to ozone levels in the PRD for episodic ozone events. Moreover, we find substantial seasonal variations in the way ozone precursors from neighboring areas affect ozone levels in any particular city, suggesting that regional collaborations are important for developing effective long‐term strategies to reduce ozone over the PRD region.
Key Points
Super‐regional contribution is dominant during non‐episode days
Local and regional sources become larger and are the main cause of ozone episodes
Mobile source is the dominant source category for ozone formation in the PRD
Summary
There is no consensus about factors that increase risk of hepatocellular carcinoma (HCC) among patients with chronic hepatitis B who have achieved seroclearance of hepatitis B surface antigen ...(HBsAg). To assess the available evidence about risk factors for HCC after HBsAg seroclearance, Scopus, EMBASE, PubMed and Cochrane Library databases were systematically searched for relevant studies published through 15 September 2017. A total of 28 studies involving more than 105 411 patients with chronic hepatitis B were included. HBsAg seroclearance occurred spontaneously in 7656, while it occurred after interferon or nucleos(t)ide analogue therapy in 1248. The rate of HBsAg seroclearance was 6.77%. Incidence of HCC was significantly lower among patients who experienced HBsAg seroclearance than among those who remained HBsAg‐positive (1.86% vs 6.56%, P < .001). Risk factors of HCC occurrence included cirrhosis (incidence with vs without: 9.51% vs 1.66%), male gender (2.34% vs 0.64%) and age ≥ 50 year at HBsAg seroclearance (2.34% vs 0.63%) (all P < .001). The available evidence suggests that HCC can develop at a low rate after HBsAg seroclearance, so periodic surveillance is recommended, especially for male patients, patients with cirrhosis and patients who experience HBsAg seroclearance when at least 50 years old.
•LaFe11.6Si1.4/Pr2Co7 composites were fabricated by SPS followed by annealing.•10 wt% Pr2Co7 addition and medium LaFe11.6Si1.4 powders were conducive to 1:13 phase formation.•The diffusion of Pr/Co ...into the 1:13 phase improves the TC of these composites.•The composites exhibit excellent (σbc)max of 930–1405 MPa and λ of 14–20.90 W/m∙K.•These composites are promising candidates for near RT cooling applications.
A series of LaFe11.6Si1.4/xwt%Pr2Co7 (x = 0, 5, 10) composites, with a range of particle size of LaFe11.6Si1.4 powders, were successfully fabricated by spark plasma sintering (SPS), followed by annealing. The influence of the particle size of the LaFe11.6Si1.4 powders and the Pr2Co7 binder content on the phase constitution, microstructure, thermal, mechanical, magnetic and magnetocaloric properties were studied. The Pr2Co7 binder content (10 wt%) and the particle size of LaFe11.6Si1.4 powders (100–200 µm) were chosen to be conducive to the formation of the desired 1:13 phase. The magnetic and magnetocaloric properties were influenced by the synergistic effects of Pr and Co atomic diffusion as well by the particle size of the LaFe11.6Si1.4 majority phase powders. The values of TC, (ΔSM)max and RC for the sample could be tuned in the range of 230–297 K, 1.90–3.70 J/kg·K and 84–149 J/kg (ΔH=2 T), respectively, by tuning the Pr2Co7 content and the particle size of the LaFe11.6Si1.4 powders. Significantly, this TC range covers a wide variety of near room temperature cooling applications. The excellent values of thermal conductivity, maximum compressive strength and strain were in the range of 14–20.90 W/m·K, 930–1405 MPa and 5.9–7.9%, respectively. These features make these materials very promising candidates for near room temperature magnetic cooling applications.
Element isotopes are characterized by distinct atomic masses and nuclear spins, which can significantly influence material properties. Notably, however, isotopes in natural materials are homogenously ...distributed in space. Here, we propose a method to configure material properties by repositioning isotopes in engineered van der Waals (vdW) isotopic heterostructures. We showcase the properties of hexagonal boron nitride (hBN) isotopic heterostructures in engineering confined photon-lattice waves-hyperbolic phonon polaritons. By varying the composition, stacking order, and thicknesses of h
BN and h
BN building blocks, hyperbolic phonon polaritons can be engineered into a variety of energy-momentum dispersions. These confined and tailored polaritons are promising for various nanophotonic and thermal functionalities. Due to the universality and importance of isotopes, our vdW isotope heterostructuring method can be applied to engineer the properties of a broad range of materials.
Display omitted
•High density La-Fe-Si based composites were fabricated by short time SPS followed by annealing.•The magnetocaloric and mechanical properties could be tuned by changing the SPS ...temperature.•The optimum process was SPS@1273 K/5min followed by annealing@1323 K/24 h.•Excellent (σbc)max ∼ 1GPa, λ ∼ 17.68 W/m∙K and large (−ΔSM)max ∼ 2.3 J/kg‧K@2T were obtained.
La(Fe,Si)13 based magnetocaloric composites were prepared by spark plasma sintering (SPS), followed by annealing. The microstructure, mechanical and magnetocaloric properties were investigated. With increasing SPS temperature (TSPS) below 1373 K, the content of (La,Pr)(Fe,Co,Si)13 majority phase increased, while the content of minority phase α-Fe decreased. The increase of TSPS from 973 K to 1373 K greatly improved the composite density, and the density sharply increased from ∼ 68 % to 98 %. After SPS at 1273 K/5 min followed by 1323 K/24 h annealing, high content of 89.35 wt% of the desired (La,Pr)(Fe,Co,Si)13 phase was obtained in LaFe11.6Si1.4/10wt%Pr2Co7 composites. A large increase of Curie temperature (TC) from 196 K to 297 K was observed. The maximum magnetic entropy change (−ΔSM)max reached 2.3 J/(kg‧K) under 2 T magnetic field. ∼ 97 % of full density, excellent compressive strength of ∼ 1GPa and high thermal conductivity of 17.68 W/m∙K were exhibited. Thus, a route to produce high density La-Fe-Si based magnetocaloric composites with excellent mechanical properties and thermal conductivity, good (−ΔSM)max and adjustable TC by short time spark plasma sintering followed by annealing was demonstrated.
PDF
