Abstract
Background
Studies have been conducted to evaluate whether sarcopenia is a predictor for survival in patients with colon cancer postsurgery, but findings have been inconsistent, and effects ...of age were seldom evaluated.
Methods
We recruited 133 patients with resectable colon cancer who underwent surgery between January 2014 and December 2017 at a teaching hospital to evaluate the effects of sarcopenia on survival, after adjusting for age and other potential predictors, including visceral adiposity (VA).
Results
Preoperative sarcopenia was associated with worse overall survival (OS: 62.3% vs. 83.8%,
p
= 0.04) and longer hospital stay (20.6 vs. 14.9 days,
p
< 0.01) while VA was not. Cox proportional hazards regressions showed that sarcopenia was associated with an adjusted hazard ratio (HR) of 2.91 (95% confidence interval CI: 1.08−7.86) after adjustment for other independent risk factors, but was not associated with disease free survival. In stratified analyses, we found that sarcopenia was an independent factor for worse OS (adjusted HR = 1.94; 95% CI: 1.11−3.38) among patients >70 years, but not among patients ≤70 years (HR = 0.48; 95% CI: 0.55−4.55).
Conclusions
Age appeared to be a modifier of the effects of sarcopenia on OS among colon cancer patients postsurgery.
This open-label phase III trial evaluated efficacy and tolerability of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC) without prior systemic therapy.
Patients ...were randomly assigned in a 1:1 ratio to linifanib 17.5 mg once daily or sorafenib 400 mg twice daily. Patients were stratified by region (Outside Asia, Japan, and rest of Asia), Eastern Cooperative Oncology Group performance score (ECOG PS; 0 or 1), vascular invasion or extrahepatic spread (yes or no), and hepatitis B virus (HBV) infection (yes or no). The primary end point of the study was overall survival (OS). Secondary end points were time to progression (TTP) and objective response rate (ORR) per RECIST v1.1.
We randomly assigned 1,035 patients (median age, 60 years; Asian, 66.6%; ECOG PS 0, 65.2%; HBV, 49.1%; vascular invasion or extrahepatic spread, 70.1%). Median OS was 9.1 months on the linifanib arm (95% CI, 8.1 to 10.2) and 9.8 months on the sorafenib arm (95% CI, 8.3 to 11.0; hazard ratio HR, 1.046; 95% CI, 0.896 to 1.221). For prespecified stratification subgroups, OS HRs ranged from 0.793 to 1.119 and the 95% CI contained 1.0. Median TTP was 5.4 months on the linifanib arm (95% CI, 4.2 to 5.6) and 4.0 months on the sorafenib arm (95% CI, 2.8 to 4.2; HR, 0.759; 95% CI, 0.643 to 0.895; P = .001). Best response rate was 13.0% on the linifanib arm versus 6.9% on the sorafenib arm. Grade 3/4 adverse events (AEs); serious AEs; and AEs leading to discontinuation, dose interruption, and reduction were more frequent with linifanib (all P < .001).
Linifanib and sorafenib had similar OS in advanced HCC. Predefined superiority and noninferiority OS boundaries were not met for linifanib and the study failed to meet the primary end point. TTP and ORR favored linifanib; safety results favored sorafenib.
There are serious questions about the grain structure of metals after laser melting and the ways that it can be controlled. In this regard, the current paper explains the grain structure of metals ...after laser melting using a new model based on combination of 3D finite element (FE) and cellular automaton (CA) models validated by experimental observation. Competitive grain growth, relation between heat flows and grain orientation and the effect of laser scanning speed on final micro structure are discussed with details. Grains structure after laser melting is founded to be columnar with a tilt angle toward the direction of the laser movement. Furthermore, this investigation shows that the grain orientation is a function of conduction heat flux at molten pool boundary. Moreover, using the secondary laser heat source (SLHS) as a new approach to control the grain structure during the laser melting is presented. The results proved that the grain structure can be controlled and improved significantly using SLHS. Using SLHS, the grain orientation and uniformity can be change easily. In fact, this method can help us to produce materials with different local mechanical properties during laser processing according to their application requirements.
Schematic of the band-gap structures of BiOF/BiOI and the possible charge separation processes.
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This is the first paper to report a series of bismuth oxyfluoride/bismuth oxyiodide ...(BiOpFq/BiOxIy) nanocomposites with different F/I molar ratios, pH values, and reaction temperatures that were synthesized through a template-free and controlled hydrothermal method. These nanocomposites were characterized through scanning electron microscope energy dispersive microscopy (SEM-EDS), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), Brunauer–Emmett–Teller (BET), and diffuse reflectance spectroscopy (DRS). Under visible-light irradiation, the BiOpFq/BiOxIy composites exhibited excellent photocatalytic activities in the degradation of crystal violet (CV) and 2-hydroxybenzoic acid (HBA). The order of rate constants was BiOF/BiOI > BiOI ≫ BiOF. The photocatalytic activity of BiOF/BiOI composites reached a maximum rate constant of 0.2305 h−1, 1.2 times higher than that of BiOI and 100 times higher than that of BiOF. Thus, the derived BiOF/BiOI is crucial for photocatalytic activity enhancement. After the removal of CV in the third cycle, no apparent deficits in photocatalytic activity were observed, and the observed deficit was 8.2% during the fifth run. Overall, the catalytic activity and stability observed for the proposed composites were determined to be adequate under visible-light irradiation. For various scavengers, the noted quenching effects demonstrated that reactive O2− has a notable role in the degradation of the applied CV.
Background
Arginine starvation depletes the micronutrients required for DNA synthesis and interferes with both thymidylate synthetase activity and DNA repair pathways in preclinical models of ...hepatocellular carcinoma (HCC). Pegylated arginine deiminase (ADI‐PEG 20), an arginine degrader, potentiates the cytotoxic activity of platinum and pyrimidine antimetabolites in HCC cellular and murine models.
Methods
This was a global, multicenter, open‐label, single‐arm, phase 2 trial of ADI‐PEG 20 and modified 5‐fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients who had HCC with Child‐Pugh A cirrhosis and disease progression on ≥2 prior lines of treatment. The primary objective was the objective response rate assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary objectives were to estimate progression‐free survival, overall survival, safety, and tolerability. Eligible patients were treated with mFOLFOX6 intravenously biweekly at standard doses and ADI‐PEG‐20 intramuscularly weekly at 36 mg/m2.
Results
In total, 140 patients with advanced HCC were enrolled. The median patient age was 62 years (range, 30‐85 years), 83% of patients were male, 76% were of Asian race, 56% had hepatitis B viremia, 10% had hepatitis C viremia, 100% had received ≥2 prior lines of systemic therapy, and 39% had received ≥3 prior lines of systemic therapy. The objective response rate was 9.3% (95% confidence interval CI, 5.0%‐15.4%), with a median response duration of 10.2 months (95% CI, 5.8 months to not reached). The median progression‐free survival was 3.8 months (95% CI, 1.8‐6.3 months), and the median overall survival was 14.5 months (95% CI, 13.6‐20.9 months). The most common grade ≥3 treatment‐related events were neutropenia (32.9%), white blood cell count decrease (20%), platelet count decrease (19.3%), and anemia (9.3%).
Conclusions
Concurrent mFOLFOX6 plus ADI‐PEG 20 exhibited limited antitumor activity in patients with treatment‐refractory HCC. The study was terminated early, and no further evaluation of the combination will be pursued.
Lay Summary
Arginine is an important nutrient for hepatocellular carcinoma (HCC).
The depletion of arginine with pegylated arginine deiminase (ADI‐PEG 20), an arginine degrader, appeared to make chemotherapy (FOLFOX) work better in animal models of HCC and in patients with HCC on an early phase clinical trial.
To formally test this hypothesis in the clinical setting, a large, global, phase 2 clinical trial was conducted of ADI‐PEG 20 and FOLFOX in the treatment of patients with refractory HCC.
The study showed limited activity of ADI‐PEG 20 and FOLFOX in advanced HCC and was stopped early.
Despite high‐level preclinical and early phase clinical data suggesting a potentiating effect of arginine depletion on 5‐fluorouracil, leucovorin, and oxaliplatin (FOLFOX) anticancer activity in hepatocellular carcinoma, a global, single‐arm, phase 2 study of pegylated arginine deiminase (ADI‐PEG 20) plus FOLFOX in patients with hepatocellular carcinoma who progressed on 2 lines of systemic therapy failed to meet its primary end point. There is no role for the combination of AGI‐PEG 20 and FOLFOX in advanced hepatocellular carcinoma.
Exosomes are implicated in cancer cell development, migration and invasion. Pigment epithelium-derived factor (PEDF) is a secreted anticancer protein that can regulate lung cancer progression; ...however, the role of PEDF in non-small cell lung cancer (NSCLC), including metastasis and cancer cell-derived exosome secretion, is unclear. In this study, we analyzed the effects of PEDF on exosome-mediated migration, invasion, and tumorigenicity of cultured NSCLC cells. The results showed that PEDF overexpression significantly reduced NSCLC invasion and migration, while inducing cell aggregation, whereas PEDF knockdown had the opposite effects. Exosomes from NSCLC cells treated with recombinant PEDF had a significantly reduced ability to promote cancer cell motility, migration, and invasion compared to exosomes from untreated cells. Exosomes from PEDF-treated cells contained thrombospondin 1 (THBS1), which inhibited cytoskeletal remodeling and exosome-induced lung cancer cell motility, migration, and invasion. Furthermore, PEDF-overexpressing NSCLC cells formed smaller xenograft tumors with higher THBS1 expression compared to control tumors. Our findings indicate that PEDF decreases the metastatic potential of NSCLC cells through regulation of THBS1 release in cancer cell-derived exosomes, thus uncovering a new mechanism of lung cancer progression.
•PEDF induces aggregation and reduces invasion and migration of lung cancer cells.•Exosomes from PEDF-treated cancer cells inhibit metastatic behavior of NSCLC cells.•PEDF-expressing NSCLC cells have reduced tumorigenicity in vivo.•PEDF increases thrombospondin 1 content in lung cancer cell-derived exosomes.•Thrombospondin 1 inhibits exosome-induced lung cancer cell migration and invasion.
PbBiO2I formation processes proposed and schematic of the band gap structures of PbBiO2I/g-C3N4.
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•This is the first report that PbBiO2I/g-C3N4 is synthesized by hydrothermal ...method.•PbBiO2I/g-C3N4 exhibit enhanced photocatalytic activities on the CV and 2-HBA degradation.•The catalytic performance illustrates the best reaction rate constant 0.3259 h−1.•These are 13.7 and 9.1 times higher than those of PbBiO2I and g-C3N4, respectively.•The results reveal that the reactive O2− plays the major roles in the CV degradation.
An ecofriendly and cheap photocatalyst is crucial for realizing practical photocatalysis applications. Many inorganic materials have modular structures in which individual units are responsible for different functions. Bi2O22+ slabs with an α-PbO-type structure and simple halide layers are effective spacers in some layered functional materials. Previous reports have mainly discussed electronic reasons for the different photocatalytic activities of layered PbBiO2X-type materials (X = Cl, Br, I). To the best of our knowledge, nanocomposite semiconductors consisting of PbBiO2I/g-C3N4 have not been reported in the literature. In this study, PbBiO2X/g-C3N4 composites were isolated and characterized by FE-SEM-EDS, XRD, HR-XPS, TEM, PL, BET, FT-IR, and UV–vis-DRS. By degrading crystal violet (CV) and 2-hydroxybenzoic acid (HBA) in an aqueous solution under visible-light irradiation, the photocatalytic activities of PbBiO2I/g-C3N4 are discussed further. In particular, the catalytic performance illustrates the best reaction rate constants of 0.3259 h−1 using the PbBiO2I/g-C3N4 composite as the photocatalysts; these are 13.7 and 9.1 times higher than those of PbBiO2I and g-C3N4, respectively. The quenching effects of different scavenger results demonstrate that reactive O2− plays the major role and OH, h+, and 1O2 play the minor role in CV degradation.
Introduction
Fracture Liaison Services (FLS) has been proven effective in reducing subsequent fractures and related mortality. However, more research is needed on the impact of FLS on the 30-day ...readmission rate and its effectiveness in rural hospitals. This study aims to assess the impact of FLS on clinical outcomes including readmission rates, subsequent fractures, and fracture-related mortality in rural areas of an Asain country.
Materials and methods
In a rural hospital in Taiwan, we conducted a two-year prospective cohort study on elderly individuals with fragility hip fractures. The study compared the clinical outcomes between the control group and the FLS-cohort group. Logistic regression analysis was used to identify factors contributing to 1-year mortality after injury.
Results
556 patients were enrolled. (304 in the control group and 252 in the FLS group) The mean age was 79.8 years. The findings revealed that the introduction of FLS did not result in significant differences in mortality, readmission, complication, subsequent fractures, or secondary hip fractures. However, there were notable improvements in the length of hospital stay and the proportion of patients receiving surgery within 48 h following the implementation of FLS. Subgroup analysis showed that FLS patients who received anti-osteoporotic treatment had lower mortality and 30-day readmission rates. Factors associated with higher 1-year mortality included male, high ASA level, and delayed surgery.
Discussion
This study provides the real-life evidence of the effect of intensive FLS model in a rural hospital in an Asian country.
Conclusion
While FLS did not show significant differences in certain clinical outcomes, it led to shorter hospital stays and increased timely surgeries. FLS patients receiving anti-osteoporotic treatment had better mortality and readmission rates. Further research is necessary to gain a comprehensive understanding of the impact of FLS care in rural areas of Asia.
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•This is the first report that PbBiO2Br/BiOBr is synthesized by hydrothermal method.•PbBiO2Br/BiOBr exhibit enhanced photocatalytic activities on the CV degradation.•The catalytic ...performance illustrates the best reaction rate constant 6.01×10−2h−1.•The results demonstrate that the reactive O2•− plays the major and OH the minor roles.
This is the first report that PbBiO2Br/BiOBr is synthesized by a template-free hydrothermal method. The composition and morphologies of the samples could be controlled by adjusting some growth parameters, including reaction pH, Pb/Bi molar ratio, and temperature. All the samples are characterized by XRD, TEM, XPS, SEM-EDS, FT-IR, BET, EPR, and UV-vis-DRS. The PbBiO2Br/BiOBr photocatalysts exhibit enhanced photocatalytic activities on the degradation of crystal violet (CV) under visible-light irradiation. In particular, the catalytic performance illustrates the best reaction rate constant 1.257×10−1h−1 once PbBiO2Br/BiOBr is used as the photocatalyst; which is 3 and 2 times higher than the reaction rate constant of PbBiO2Br and BiOBr being the photocatalysts, respectively. This study reveals that PbBiO2Br/BiOBr can be used to suppress the recombination of photoinduced electron-hole pairs and contribute to the enhanced photocatalytic efficiency of semiconductors in the visible-light-driven catalysis. The possible photodegradation mechanism is studied by examining different active species through EPR and adding appropriate scavengers. The results demonstrate that the reactive O2− plays the major and OH the minor roles in the CV degradation.
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