Display omitted
•Aqueous extract of Cystoseira baccata served to synthesize gold nanoparticles Au@CB.•Au@CB are spherical polycrystalline nanoparticles with a mean diameter of 8.4nm.•Au@CB exhibit ...strong cytotoxicity against Caco-2 and HT-29 and no effect on the healthy cells.•Au@CB induce apoptosis activation by the extrinsic and mitochondrial pathway.
This study is the first dealt with the use of brown macroalgae Cystoseira baccata (CB) extracts in obtaining gold nanoparticles (Au@CB) through an eco-friendly, fast, one-pot synthetic route. The formation of spherical, stable, polycrystalline nanoparticles with mean diameter of 8.4±2.2nm was demonstrated by UV–vis spectroscopy, TEM, HRTEM, STEM and zeta potential measurements. The extract appears to act as a protective agent where the particles are embedded, keeping them separated, avoiding aggregation and coalescence. The EELS and EDS analyses confirmed the elemental composition of the extract and nanoparticles. Moreover, the functional group of biomolecules present in CB and Au@CB were characterized by FTIR. The effects of CB extract and Au@CB were tested in vitro on the colon cancer cell lines HT-29 and Caco-2, as well as on normal primary neonatal dermal fibroblast cell line PCS-201-010. Results show a stronger cytotoxic effect against HT-29 than that on Caco-2; interestingly, a lack of toxicity on PCS-201-010 was obtained. Finally, the apoptotic activity was determined; Au@CB is able to induce apoptosis activation by the extrinsic and mitochondrial pathway in our CRC in vitro model. These encouraging results suggest that Au@CB has a significant potential for the treatment of colon rectal cancer.
Summary
Background
Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline ...phosphatase ALP and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long‐term effectiveness of second‐line treatments remains uncertain.
Aims
To evaluate the long‐term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation).
Methods
We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non‐responsive PBC patients (Paris‐II criteria) from Spain and Portugal who received OCA ± fibrates.
Results
Of 255 patients, median follow‐up was 35.1 months (IQR: 20.2–53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE‐PBC and 5‐year UK‐PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension.
Conclusion
Triple therapy was superior in achieving therapeutic goals in UDCA‐nonresponsive PBC. Decompensation was linked to pre‐existing portal hypertension.
Longitudinal, real‐world study on 255 UDCA‐nonresponsive PBC patients (Per Paris II criteria); median follow‐up of 35.1 months (IQR: 20–53). All patients received obeticholic acid (OCA), with 25% receiving later add‐on fibrate treatment (triple therapy). In multivariate analysis, triple therapy outperformed dual therapy across all surrogate biochemical endpoints of outcomes.
Low muscle mass is a common condition in the critically ill population and is associated with adverse clinical outcomes. The primary aim of this study was to analyze the prognostic significance of ...low muscle mass using computed tomography (CT) scans in COVID-19 critically ill patients. A second objective was to determine the accuracy and agreement in low muscle mass identification using diverse markers compared to CT as the gold standard.
This was a prospective cohort study of COVID-19 critically ill patients. Skeletal muscle area at the third lumbar vertebra was measured. Clinical outcomes (intensive care unit ICU and hospital length of stay LOS, tracheostomy, days on mechanical ventilation MV, and in-hospital mortality) were assessed. Phase angle, estimated fat-free mass index, calf circumference, and mid-upper arm circumference were measured as surrogate markers of muscle mass.
Eighty-six patients were included (mean age ± SD: 48.6 ± 12.9; 74% males). Patients with low muscle mass (48%) had a higher rate of tracheostomy (50 vs 20%, p = 0.01), prolonged ICU (adjusted HR 0.53, 95%CI 0.30–0.92, p = 0.024) and hospital LOS (adjusted HR 0.50, 95% CI 0.29–0.86, p = 0.014). Bedside markers of muscle mass showed poor to fair agreement and accuracy compared to CT-assessed low muscle mass.
Low muscle mass at admission was associated with prolonged length of ICU and hospital stays. Further studies are needed to establish targeted nutritional interventions to halt and correct the catabolic impact of COVID-19 in critically ill patients, based on standardized and reliable measurements of body composition.
In the phase III KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed–platinum) significantly improved overall survival (OS) and progression-free ...survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) versus placebo plus pemetrexed–platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed–platinum and in patients who completed 35 cycles (∼2 years) of pembrolizumab.
Eligible patients were randomized 2 : 1 to receive pembrolizumab 200 mg (n = 410) or placebo (n = 206) every 3 weeks (for up to 35 cycles, ∼2 years) plus four cycles of pemetrexed (500 mg/m2) and investigators’ choice of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg·min/ml) every 3 weeks, followed by pemetrexed until progression. Patients assigned to placebo plus pemetrexed–platinum could cross over to pembrolizumab upon progression if eligibility criteria were met. The primary endpoints were OS and PFS.
After a median follow-up of 31.0 months, pembrolizumab plus pemetrexed–platinum continued to improve OS hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.46-0.69 and PFS (HR, 0.49; 95% CI, 0.41-0.59) over placebo plus pemetrexed–platinum regardless of programmed death-ligand 1 expression. Objective response rate (ORR) (48.3% versus 19.9%) and time to second/subsequent tumor progression on next-line treatment (PFS2; HR, 0.50; 95% CI, 0.41-0.61) were improved in patients who received pembrolizumab plus pemetrexed–platinum. Eighty-four patients (40.8%) from the placebo plus pemetrexed–platinum group crossed over to pembrolizumab on-study. Grade 3-5 adverse events occurred in 72.1% of patients receiving pembrolizumab plus pemetrexed–platinum and 66.8% of patients receiving placebo plus pemetrexed–platinum. Fifty-six patients completed 35 cycles (∼2 years) of pembrolizumab; ORR was 85.7% and 53 (94.6%) were alive at data cut-off.
Pembrolizumab plus pemetrexed–platinum continued to show improved efficacy outcomes compared with placebo plus pemetrexed–platinum, with manageable toxicity. These findings support first-line pembrolizumab plus pemetrexed–platinum in patients with previously untreated metastatic nonsquamous NSCLC.
•KEYNOTE-189 evaluated the efficacy and safety of pembrolizumab + pemetrexed–platinum versus placebo + pemetrexed–platinum in NSCLC.•Pembrolizumab + pemetrexed–platinum improved OS (HR, 0.56; 95% CI, 0.46-0.69) versus placebo + pemetrexed–platinum.•Pembrolizumab + pemetrexed–platinum improved PFS (HR, 0.49; 95% CI, 0.41-0.59) versus placebo + pemetrexed–platinum.•ORR was 85.7% in patients who completed 35 cycles (2 years) of pembrolizumab therapy.•Pembrolizumab + pemetrexed–platinum had manageable toxicity.
LINKED CONTENT
This article is linked to Gomez et al papers. To view these articles, visit https://doi.org/10.1111/apt.18004 and https://doi.org/10.1111/apt.18032
Summary
Background
Grey Zone (GZ) is an ill‐defined situation including patients falling between inactive carrier (IC) state and HBeAg‐negative chronic hepatitis B (HBeAg‐negative CHB).
Aims
To ...assess the long‐term outcomes of GZ patients compared to IC in the absence of treatment.
Methods
Retrospective analysis of 287 IC and GZ HBeAg‐negative patients. Patients were classified into 4 groups at baseline: HBV‐DNA <2000 IU/mL and ALT <40 U/L (IC), HBV‐DNA <2000 IU/mL and ALT 40‐80 U/L (GZ‐1), HBV‐DNA 2000‐20 000 IU/mL and ALT <40 U/L (GZ‐2) or ALT 40‐80 U/L (GZ‐3). Data were also analysed using AASLD ALT criteria.
Results
After a median follow‐up of 8.2 (5‐19) years, HBsAg loss occurred in about 15% ICs or GZ patients. Transition into IC state occurred in 40% of GZ patients. DNA fluctuations >2000 IU/mL correlated inversely with transition into IC and HBsAg loss. HBsAg levels were significantly lower in ICs than in GZ patients (338 IU/mL 20‐3269 vs 5763 IU/mL 2172‐17 754; P < 0.05). Among the latter group, there was an increasing gradient of HBsAg levels from GZ‐1 to GZ‐3 patients (P < 0.05). HBeAg‐negative CHB occurred in only 18 (6.3%) GZ patients. No patient developed cirrhosis nor advanced fibrosis. ALT/HBV‐DNA fluctuations and HBeAg‐negative CHB development were more frequent in genotype B/C patients, whereas HBsAg loss occurred only in genotype A/D patients.
Conclusions
Most Caucasian GZ patients present excellent long‐term outcomes in the absence of treatment, with a high rate of HBsAg loss and low rate of progression to HBeAg‐negative CHB. HBV‐genotyping and HBsAg levels could help to predict outcomes and better classify GZ patients.
Linked ContentThis article is linked to Ridruejo paper. To view this article visit https://doi.org/10.1111/apt.14644.
The technological development of quantum dots has ushered in a new era in fluorescence bioimaging, which was propelled with the advent of novel multiphoton fluorescence microscopes. Here, the ...potential use of CdSe quantum dots has been evaluated as fluorescent nanothermometers for two-photon fluorescence microscopy. In addition to the enhancement in spatial resolution inherent to any multiphoton excitation processes, two-photon (near-infrared) excitation leads to a temperature sensitivity of the emission intensity much higher than that achieved under one-photon (visible) excitation. The peak emission wavelength is also temperature sensitive, providing an additional approach for thermal imaging, which is particularly interesting for systems where nanoparticles are not homogeneously dispersed. On the basis of these superior thermal sensitivity properties of the two-photon excited fluorescence, we have demonstrated the ability of CdSe quantum dots to image a temperature gradient artificially created in a biocompatible fluid (phosphate-buffered saline) and also their ability to measure an intracellular temperature increase externally induced in a single living cell.
•Combined pollution with copper nanoparticles and atrazine in soil is studied.•Isotherms demonstrate that atrazine adsorption is favored by the presence of copper nanoparticles.•Copper nanoparticles ...decrease atrazine dissipation.•Combined pollution not alter the soil microbial communities.
Copper nanoparticles (NCu) have been proposed as an antimicrobial agent in agriculture. Therefore, NCu may interact with numerous pollutants including pesticides. Little is known about the combined effects of NCu and pesticides in soil. This study aimed at assessing the impact of NCu combined with the herbicide atrazine (ATZ) on soil. We focused on assessing the adsorption and dissipation of ATZ in the presence of NCu and the changes in microbial community profiles. First, ATZ adsorption isotherms (described using the Freundlich equation) were evaluated. After that, soil samples were spiked with NCu (40–60 nm) at 0.05 and 0.15% w/w and ATZ (3 mg a.i kg−1) and incubated for 30 days. The results showed that ATZ adsorption is favored by the presence of NCu. On the other hand, NCu at 0.15% w/w caused a significant decrease in ATZ dissipation, increasing its half-life from 6 to 37 days. Microbial community profiles (bacteria, fungi and nitrifying bacteria) remained relatively stable throughout the evaluated period. Therefore, our findings suggest that NCu can increase the persistence of ATZ in soil, which may be mostly associated to physical-chemical interaction with soil particles more than a microbial impact.
To assess the quality of antifungal use, to propose a point score for this evaluation and to estimate the potential economic savings of an antifungal stewardship programme.
From December 2010 to ...January 2011, we identified 100 adult inpatients receiving systemic antifungals. Antifungal use was evaluated by means of a predefined score that considered indication, drug selection, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. Total antifungal prescriptions in defined daily doses (DDDs) and days of therapy (DOTs) and potential cost savings were calculated.
Overall, 43% of prescriptions came from medical departments, 25% from haematology/oncology and 17% from intensive care units. The main reasons for starting antifungals were empirical (42%), pre-emptive (20%) and targeted treatment (20%). Antifungals were unnecessary in 16% of cases. Inadequacies in other aspects of antifungal prescription were: drug selection, 31%; dosing, 16%; no switch from intravenous to oral administration, 20%; no adjustment after microbiological results, 35%; and length of therapy, 27%. The number of antifungal DDDs per 1000 patient-days was 65.1. The total number of DOTs was 1556, which added a direct cost of €219 364. Only 51.3% of DOTs were considered optimal. The potential estimated savings would be €50 536.
Major efforts should be made to improve the selection and duration of antifungal therapy. Our study demonstrated the potential cost savings that could be achieved by optimizing antifungal therapy. A stewardship programme should include an instrument to objectively evaluate the adequacy of antifungal use.
Context
Most protected areas are managed based on objectives related to scientific ecological knowledge of species and ecosystems. However, a core principle of sustainability science is that ...understanding and including local ecological knowledge, perceptions of ecosystem service provision and landscape vulnerability will improve sustainability and resilience of social-ecological systems. Here, we take up these assumptions in the context of protected areas to provide insight on the effectiveness of nature protection goals, particularly in highly human-influenced landscapes.
Objectives
We examined how residents’ ecological knowledge systems, comprised of both local and scientific, mediated the relationship between their characteristics and a set of variables that represented perceptions of ecosystem services, landscape change, human-nature relationships, and impacts.
Methods
We administered a face-to-face survey to local residents in the Sierra de Guadarrama protected areas, Spain. We used bi- and multi-variate analysis, including partial least squares path modeling to test our hypotheses.
Results
Ecological knowledge systems were highly correlated and were instrumental in predicting perceptions of water-related ecosystem services, landscape change, increasing outdoors activities, and human-nature relationships. Engagement with nature, socio-demographics, trip characteristics, and a rural–urban gradient explained a high degree of variation in ecological knowledge. Bundles of perceived ecosystem services and impacts, in relation to ecological knowledge, emerged as social representation on how residents relate to, understand, and perceive landscapes.
Conclusions
Our findings provide insight into the interactions between ecological knowledge systems and their role in shaping perceptions of local communities about protected areas. These results are expected to inform protected area management and landscape sustainability.
PDF
