HER2 positive rates are enriched amongst colorectal cancer brain metastases: a study amongst 1920 consecutive patients

Temozolomide and irinotecan (TEMIRI regimen) as salvage treatment of irinotecan-sensitive advanced colorectal cancer patients bearing MGMT methylation

Abstract

Background

Non-randomized studies showed that temozolomide (TMZ) achieves an average 10% response rate in heavily pretreated metastatic colorectal cancer (mCRC) patients with promoter methylation of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT). In this phase II trial, irinotecan and temozolomide (TEMIRI) combination regimen was assessed in irinotecan-sensitive, MGMT methylated/microsatellite stable (MSS) pretreated mCRC patients.

Patients and methods

Key inclusion criteria were: centrally confirmed MGMT methylation by methylation-specific PCR, MSS mCRC, progression after at least two prior chemotherapy regimens for advanced disease and irinotecan-free interval (IFI) >3 months. TEMIRI (TMZ 150mg/sqm on days 1-5 plus irinotecan 100mg/sqm on days1,15 q28 days) was administered for six cycles, followed by maintenance with TMZ. The primary endpoint was overall response rate (ORR). Exploratory translational analyses included MGMT immunoistochemistry (IHC) and methylBEAMing (MB).

Results

Between December 2014 and June 2017, 25 patients were enrolled. The primary endpoint was met, since 6 patients achieved a partial response (ORR 24%, 95% CI, 11%-43%). At a median follow-up of 15.6 months, median progression-free survival (mPFS) and overall survival (mOS) were 4.4 and 13.8 months, respectively. Only 4 (16%) patients had ≥ grade 3 adverse events. All patients whose cancer was MGMT-positive IHC were non-responders. Consistently, patients with MGMT-negative/low tumors had a significantly longer mPFS than others (6.9 versus 2.0 months; HR = 0.29, 95%CI, 0.02-0.41; p = 0.003) and a non-significant trend for longer mOS. MB testing showed similar accuracy.

Conclusions

TEMIRI regimen is a safe and active option in pre-treated, irinotecan-sensitive mCRC patients with MGMT methylation.

Validation of the Complexity INdex in SARComas prognostic signature on formalin-fixed, paraffin-embedded, soft tissue sarcomas

Abstract

Background

Prediction of metastatic outcome in sarcomas is challenging for clinical management since they are aggressive and carry a high metastatic risk. A 67-gene expression signature, the Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor than the reference pathological grade. Since it cannot be applied easily in standard laboratory practice, we assessed its prognostic value using nanoString on formalin-fixed, paraffin-embedded (FFPE) blocks to evaluate its potential in clinical routine practice and guided therapeutic management.

Methods

A code set consisting of 67 probes derived from the 67 genes of the CINSARC signature was built and named NanoCind®. To compare the performance of RNA-seq and nanoString (NanoCind®), we used expressions of various sarcomas (n=124, frozen samples) using both techniques and compared predictive values based on CINSARC risk groups and clinical annotations. We also used nanoString on FFPE blocks (n=67) and matching frozen and FFPE samples (n=45) to compare their level of agreement. Metastasis-free survival and agreement values in classification groups were evaluated.

Results

CINSARC strongly predicted metastatic outcome using nanoString on frozen samples (HR = 2.9, 95% CI 1.23-6.82) with similar risk-group classifications (86%). While more than 50% of FFPE blocks were not analyzable by RNA-seq owing to poor RNA quality, all samples were analyzable with nanoString. When similar (risk-group) classifications were measured with frozen tumors (RNA-seq) compared to FFPE blocks (84% agreement), the CINSARC signature was still a predictive factor of metastatic outcome with nanoString on FFPE samples (HR = 4.43, 95% CI 1.25-15.72).

Conclusion

CINSARC is a material-independent prognostic signature for metastatic outcome in sarcomas and outperforms histological grade. Unlike RNA-seq, nanoString is not influenced by the poor quality of RNA extracted from FFPE blocks. The CINSARC signature can potentially be used in combination with nanoString (NanoCind^®) in routine clinical practice on FFPE blocks to predict metastatic outcome.

Mimickers of Urticaria: Urticarial Vasculitis and Autoinflammatory Diseases

Publication date: Available online 2 June 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Mark D.P. Davis, Jeroen C.H. van der Hilst
A wide differential diagnosis must be considered in a patient presenting with urticarial plaques. Although acute and chronic urticaria are the commonest diagnoses, other differential diagnoses include polymorphous eruption of pregnancy, mast cell disorders, hypereosinophilic syndrome, urticarial vasculitis, pemphigoid, systemic lupus erythematosus, and autoinflammatory disease. This review will specifically address urticarial vasculitis and autoinflammatory syndromes. These entities represent contrasting examples of urticarial-like lesions resulting from either an adaptive immune complex–mediated mechanism (urticarial vasculitis) or an innate immune–mediated mechanism (autoinflammatory disorders), with differing therapeutic implications. In patients presenting with painful, persistent plaques that last more than 24 hours and resolve with bruising of the skin, consideration should be given to a diagnosis of urticarial vasculitis. A biopsy should be obtained to ascertain this diagnosis. In patients presenting with a persistent history of recurrent urticarial plaques associated with signs of systemic inflammation including fevers and elevated inflammatory markers (C-reactive protein [CRP]/serum amyloid A, leukocytosis, and negative connective tissue serologies), consideration should be given to autoinflammatory disorders: the 3 cryopyrin-associated periodic syndromes, Schnitzler syndrome, and familial cold autoinflammatory syndrome 2. Serum protein electrophoresis should be checked to rule out an underlying monoclonal gammopathy.

Consenso multidisciplinar sobre prevención y tratamiento de la tuberculosis en pacientes candidatos a tratamiento biológico. Adaptación al paciente dermatológico

Publication date: Available online 2 June 2018
Source:Actas Dermo-Sifiliográficas
Author(s): P. Rodríguez-Jiménez, I. Mir-Viladrich, P. Chicharro, G. Solano-López, F.J. López-Longo, C. Taxonera, P. Sánchez-Martínez, X. Martínez-Lacasa, M. García-Gasalla, J. Dorca, M. Arias-Guillén, J.M. García-García, E. Dauden
El riesgo de infección por Mycobacterium tuberculosis se halla aumentado en los pacientes con enfermedades inflamatorias crónicas y en tratamiento inmunosupresor, en particular con terapia antifactor de necrosis tumoral α. La detección de la infección tuberculosa latente y el tratamiento preventivo dirigido a reducir el riesgo de progresión a tuberculosis activa es obligatoria en este grupo de pacientes. Este documento de consenso multidisciplinar actualiza la opinión de expertos y establece recomendaciones para el diagnóstico y tratamiento de la infección tuberculosa latente en estos pacientes, según los conocimientos actuales en terapias biológicas.Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents.

Comparative study of Gram-negative bacteria response to solar photocatalytic inactivation

Abstract

Solar photocatalytic inactivation of Gram-negative bacteria with immobilized TiO₂-P25 in a fixed-bed reactor was modeled with simplified kinetic equations. The kinetic parameters are the following: the photocatalytic inactivation coefficient (k_d,QUV), the initial bacterial reduction rate (A) in the contact with the disinfecting agent, and the threshold level of damage (n) were determined to report the effect of Q_UV/TiO₂-P25 on bacterial cultivability and viability and to compare the response of bacterial strains to photocatalytic treatment. In addition, the integration of the reactivation coefficient (C_r) in the photocatalytic inactivation equation allowed evaluating the ability of bacterial reactivation after photocatalytic stress. Results showed different responses of the bacteria strains to photocatalytic stress and the ability of certain bacterial strains such as Escherichia coli ATCC25922 and Pseudomonas aeruginosa ATCC4114 to resuscitate after photocatalytic treatment.

Herbicides in vineyards reduce grapevine root mycorrhization and alter soil microorganisms and the nutrient composition in grapevine roots, leaves, xylem sap and grape juice

Abstract

Herbicides are increasingly applied in vineyards worldwide. However, not much is known on potential side effects on soil organisms or on the nutrition of grapevines (Vitis vinifera). In an experimental vineyard in Austria, we examined the impacts of three within-row herbicide treatments (active ingredients: flazasulfuron, glufosinate, glyphosate) and mechanical weeding on grapevine root mycorrhization; soil microorganisms; earthworms; and nutrient concentration in grapevine roots, leaves, xylem sap and grape juice. The three herbicides reduced grapevine root mycorrhization on average by 53% compared to mechanical weeding. Soil microorganisms (total colony-forming units, CFU) were significantly affected by herbicides with highest CFUs under glufosinate and lowest under glyphosate. Earthworms (surface casting activity, density, biomass, reproduction) or litter decomposition in soil were unaffected by herbicides. Herbicides altered nutrient composition in grapevine roots, leaves, grape juice and xylem sap that was collected 11 months after herbicide application. Xylem sap under herbicide treatments also contained on average 70% more bacteria than under mechanical weeding; however, due to high variability, this was not statistically significant. We conclude that interdisciplinary approaches should receive more attention when assessing ecological effects of herbicides in vineyard ecosystems.

The effect of anthropogenic activities on the phosphorus-buffering intensity of the two contrasting rivers in northern China

Abstract

The phosphorus (P)-buffering ability of suspended particulate matter (SPM) from the Ziya River Mainstream (ZRM) and the Luanhe River (LR) of northern China was investigated in this study. Forty samples of SPM from the ZRM and LR were collected in October and November of 2016. The ZRM has slow flow and poor water quality, while the LR has fast flow and reasonably good water quality. Under a scanning electron microscope, the SPM from the ZRM had a more complex microstructure than that from the LR, perhaps because of the slower flow and heavier pollution in the ZRM. P fractions in both SPM and water samples were determined using standard measurement and testing program methods. The equilibrium P concentration was used to determine the influence of SPM on soluble reactive P (SRP) concentrations. These SRP fractions were used to evaluate the P-buffering intensity of the two rivers. Differences in SPM microstructure resulted in the SPM from ZRM having a stronger P-buffering ability than the LR, making SPM an effective vector for SRP. Anthropogenic activities likely contributed to the differences in both microstructures of the SPM and P-buffering intensity of the rivers. A conceptual model was developed to show how anthropogenic activities influence the P-buffering intensity of the two rivers. As far as we know, this is the first time that the P-buffering intensity has been compared between two rivers that have been severely impacted by anthropogenic activities. Our findings provide an important reference for similar rivers worldwide.

Is skewed income distribution good for environmental quality? A comparative analysis among selected BRICS countries

Abstract

A large number of studies have examined the linkage between income inequality and environmental quality at the individual country levels. This study attempts to examine the linkage between the two factors for the individual BRICS economies from a comparative perspective, which is scarce in the literature. It examines the selected countries (Brazil, India, China and South Africa) by endogenising the patterns of primary energy consumption (coal use and petroleum use), total primary energy consumption, economic growth, and urbanisation as key determining factors in CO₂ emission function. The long-run results based on ARDL bounds testing revealed that income inequality leads to increase in CO₂ emissions for Brazil, India and China, while the same factor leads to reduction in CO₂ emissions for South Africa. However, it observes that while coal use increases CO₂ emissions for India, China and South Africa, it has no effect for Brazil. In contrast, the use of petroleum products contributes to CO₂ emissions in Brazil, while the use of the same surprisingly results in reduction of carbon emissions in South Africa, India and China. The findings suggest that given the significance of income inequality in environmental pollution, the policy makers in these emerging economies have to take into consideration the role of income inequality, while designing the energy policy to achieve environmental sustainability.

Reply to the letter to the editor by Swarthout et al. (2018): Comments for Mertens et al. (2018), Glyphosate, a chelating agent—relevant for ecological risk assessment?

Phthalate exposure as a risk factor for hypertension

Abstract

Phthalates are ubiquitous in environment. Hypertension is a major risk factor for cardiovascular diseases. Phthalate exposure is associated with hypertension in multiple studies. This review aims to summarize the scientific literature on associations between phthalate exposure and hypertension and discuss the mechanisms in the relationship. We identified and reviewed original articles published to March 2018, using PubMed and Web of Science to search the terms "phthalate(s)," "phthalic acid," "blood pressure," "high blood pressure," "hypertension," "prehypertension," and "cardiovascular disease." Findings were summarized based on the relevance to the themes, including presentation of main phthalates and their major metabolites as well as associations of phthalate exposure with blood pressure in epidemiological and experimental studies. We identified ten population-based investigations and five toxicological experiments. Epidemiological data underscored a possible correlation between phthalate exposure and hypertension in adults, whereas individual study in children stands on the opposite. Experimental studies mainly targeted the increasing effect of phthalates on blood pressure. This review suggested some underlying mechanisms of phthalate-associated hypertension. Considering the current evidence, phthalate might be risk factors of hypertension. However, the effect of phthalate exposure in early life on blood pressure in later life or adulthood is still unclear. Well-designed longitudinal and molecular mechanism studies are indispensable.

Spent MgO-carbon refractory bricks as a material for permeable reactive barriers to treat a nickel- and cobalt-contaminated groundwater

Abstract

Spent magnesia (MgO)-carbon refractory bricks were repurposed as a permeable reactive barrier reactive media to treat a nickel (5 mg l⁻¹)- and cobalt (0.3 mg l⁻¹)-contaminated groundwater. MgO has been used for decades as a heavy metal precipitating agent as it hydrates and buffers the pH in a range of 8.5–10 associated with the minimum solubility of various divalent metals. The contaminated groundwater site's conditions are typical of contaminated neutral drainage with a pH of 6 as well as high concentrations of iron (220 mg l⁻¹) and sulphates (2500 mg l⁻¹). Using synthetic contaminated water, batch and small-scale column tests were performed to determine the treatment efficiency and longevity. The increase and stabilization of the pH at 10 observed during the tests are associated with the hydration and dissolution of the MgO and promoted the removal not only of a significant proportion of the contaminants but also of iron. During the column test, this accumulation of precipitates over time clogged and passivated the MgO resulting in a loss of chemical performance (pH lowering, metal breakthrough) after 210 pore volumes of filtration. Precipitation also affected the hydraulic conductivity values which dropped from 2.3·10⁻³ to 4.2·10⁻⁴ m s⁻¹ at the end of test. Saturation indices and XRD analyses suggest the precipitates formed are likely composed of goethite as well as iron, cobalt and nickel hydroxides. Recycled MgO-C refractory bricks were demonstrated to be an efficient reactive material for the removal of Co and Ni, but careful considerations should be taken of the potential clogging and passivation phenomena given particular physicochemical conditions.

Soft Ethics: Its Application to the General Data Protection Regulation and Its Dual Advantage

Anthropogenic CO 2 emissions from a megacity in the Yangtze River Delta of China

Abstract

Anthropogenic CO₂ emissions from cities represent a major source contributing to the global atmospheric CO₂ burden. Here, we examined the enhancement of atmospheric CO₂ mixing ratios by anthropogenic emissions within the Yangtze River Delta (YRD), China, one of the world's most densely populated regions (population greater than 150 million). Tower measurements of CO₂ mixing ratios were conducted from March 2013 to August 2015 and were combined with numerical source footprint modeling to help constrain the anthropogenic CO₂ emissions. We simulated the CO₂ enhancements (i.e., fluctuations superimposed on background values) for winter season (December, January, and February). Overall, we observed mean diurnal variation of CO₂ enhancement of 23.5~49.7 μmol mol⁻¹, 21.4~52.4 μmol mol⁻¹, 28.1~55.4 μmol mol⁻¹, and 29.5~42.4 μmol mol⁻¹ in spring, summer, autumn, and winter, respectively. These enhancements were much larger than previously reported values for other countries. The diurnal CO₂ enhancements reported here showed strong similarity for all 3 years of the study. Results from source footprint modeling indicated that our tower observations adequately represent emissions from the broader YRD area. Here, the east of Anhui and the west of Jiangsu province contributed significantly more to the anthropogenic CO₂ enhancement compared to the other sectors of YRD. The average anthropogenic CO₂ emission in 2014 was 0.162 (± 0.005) mg m⁻² s⁻¹ and was 7 ± 3% higher than 2010 for the YRD. Overall, our emission estimates were significantly smaller (9.5%) than those estimated (0.179 mg m⁻² s⁻¹) from the EDGAR emission database.

Converting environmental risks to benefits by using spent coffee grounds (SCG) as a valuable resource

Abstract

Coffee is perhaps one of the most vital ingredients in humans' daily life in modern world. However, this causes the production of million tons of relevant wastes, i.e., plastic cups, aluminum capsules, coffee chaff (silver skin), and spent coffee grounds (SCG), all thrown untreated into landfills. It is estimated that 1 kg of instant coffee generates around 2 kg of wet SCG; a relatively unique organic waste stream, with little to no contamination, separated directly in the source by the coffee shops. The produced waste has been under researchers' microscope as a useful feedstock for a number of promising applications. SCG is considered a valuable, nutrients rich source of bioactive compounds (e.g., phenolics, flavonoids, carotenoids, lipids, chlorogenic and protocatechuic acid, melanoidins, diterpenes, xanthines, vitamin precursors, etc.) and a useful resource material in other processes (e.g., soil improver and compost, heavy metals absorbent, biochar, biodiesel, pellets, cosmetics, food, and deodorization products). This paper aims to provide a holistic approach for the SCG waste management, highlighting a series of processes and applications in environmental solutions, food industry, and agricultural sector. Thus, the latest developments and approaches of SCG waste management are reviewed and discussed.

Nanostructured catalysts applied to degrade atrazine in aqueous phase by heterogeneous photo-Fenton process

Abstract

SBA-15 and KIT-6 materials have been synthesized and modified with iron salts by the wet impregnation method with different metal loadings. The different mesostructures obtained were characterized by N₂ adsorption–desorption at 77 K, X-ray diffraction, temperature-programmed reduction, and ultraviolet–visible spectroscopy. These iron-containing mesostructured materials have been successfully tested for the heterogeneous photo-Fenton degradation of aqueous solutions of dangerous herbicides, such as atrazine, using UV–visible light irradiation, at room temperature and close to neutral pH. The results showed that the Fe/SBA-15 (10%) and Fe/KIT-6 (5%) catalysts exhibited the highest activities. However, the Fe/KIT-6 (5%) catalyst with minor Fe loading than Fe/SBA-15 (10%) presented a higher degradation of atrazine (above 98% in a reaction time of 240 min). Therefore, the interconnectivity of the cage-like mesopores had an important influence on the catalytic activity, favoring probably mass-transfer effects. Thus, the high performance of these materials indicates that the heterogeneous via of photo-Fenton process can also be efficiently employed to treat wastewaters containing pollutants such as herbicides, in order to reduce them to simplest and less toxic molecules.

Bismuth vanadate-based semiconductor photocatalysts: a short critical review on the efficiency and the mechanism of photodegradation of organic pollutants

Abstract

The number of publications on photocatalytic bismuth vanadate-based materials is constantly increasing. Indeed, bismuth vanadate is gaining stronger interest in the photochemical community since it is a solar-driven photocatalyst. However, the efficiency of BiVO₄-based photocatalyst under sunlight is questionable: in most of the studies investigating the photodegradation of organic pollutants, only few works identify the by-products and evaluate the real efficiency of BiVO₄-based materials. This short review aims to (i) present briefly the principles of photocatalysis and define the photocatalytic efficiency and (ii) discuss the formation of reactive species involved in the photocatalytic degradation process of pollutants and thus the corresponding photodegradation mechanism could be determined. All these points are developed in a comprehensive discussion by focusing especially on pure, doped, and composite BiVO₄. Therefore, this review exhibits a critical overview on different BiVO₄-based photocatalytic systems with their real efficiency. This is a necessary knowledge for potential implementation of BiVO₄ materials in environmental applications at larger scale than laboratory conditions.

Wintertime characteristic of peroxyacetyl nitrate in the Chengyu district of southwestern China

Abstract

Atmospheric concentrations of peroxyacetyl nitrate (PAN) were measured in Ziyang in December 2012 to provide basic knowledge of PAN in the Chengyu district and offer recommendations for air pollution management. The PAN pollution was relatively severe in Ziyang in winter, with the maximum and average PAN concentrations of 1.61 and 0.55 ppbv, respectively, and a typical single-peak diurnal trend in PAN and theoretical PAN lost by thermal decomposition (TPAN) were observed. PAN and O₃ concentrations were correlated (R² = 0.52) and the ratios of daily maximum PAN to O₃ ([PAN]/[O₃] ratio) ranged from 0.013 to 0.108, with an average of 0.038. Both acetone and methyl ethyl ketone (MEK) were essential for producing the acetylperoxy radicals (PA) and subsequently PAN in Ziyang in winter, and PAN concentrations at the sampling site exhibited more sensitivity to volatile organic compound (VOC) concentrations than nitrogen oxide (NO_x) levels. Therefore, management should focus on reducing VOCs emissions, in particular those that produce acetone and MEK through photolysis and oxidizing reactions. In addition, the influence of relative humidity (RH) on the heterogeneous reactions between PAN and PM_2.5 in the atmospheric environment may have led to the strong correlation between observed PM_2.5 and PAN in Ziyang in winter. Furthermore, a typical air pollution event was observed on 17–18 December 2012, which Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) and PSCF simulations suggest that it was caused by the local formation and the regional transport of polluted air masses from Hanzhong, Nanchong, and Chengdu.

Boosting the catalytic activity of natural magnetite for wet peroxide oxidation

Abstract

This work explores the modification of naturally occurring magnetite by controlled oxidation (200–400 °C, air atmosphere) and reduction (300–600 °C, H₂ atmosphere) treatments with the aim of boosting its activity in CWPO. The resulting materials were fully characterized by XRD, XPS, TGA, TPR, SEM, and magnetization measurements, allowing to confirm the development of core-shell type structures. The magnetite core of the solid remained unchanged upon the treatment whereas the Fe(II)/Fe(III) ratio of the shell was modified (e.g. 0.42, 0.11 and 0.63 values were calculated for pristine Fe₃O₄, Fe₃O₄-O400, and Fe₃O₄-R400, respectively). The performance of the catalysts was tested in the CWPO of sulfamethoxazole (SMX) (5 mg L⁻¹) under ambient conditions and circumneutral pH (pH₀ = 5), using the stoichiometric dose of H₂O₂ (25 mg L⁻¹) and a catalyst load of 1 g L⁻¹. The key role of the ferrous species on the mineral shell was evidenced. Whereas the oxidation of magnetite led to significantly slower degradation rates of the pollutant, its reduction gave rise to a dramatic increase, achieving the complete removal of SMX in 1.5 h reaction time with the optimum catalyst (Fe₃O₄-R400) compared to the 3.5 h required with the pristine mineral. A reaction mechanism was proposed for SMX degradation, and a kinetic equation based on the Eley-Rideal model was accordingly developed. This model successfully fitted the experimental results. The stability of Fe₃O₄-R400 was evaluated upon five sequential runs. Finally, the versatility of the catalytic system was proved in real environmentally relevant water matrices.

CFD modeling of a UV-A LED baffled flat-plate photoreactor for environment applications: a mining wastewater case

Abstract

The use of ultraviolet light in photoreactors for wastewater treatment has become popular as an alternative of known chemical oxidative substances. UV LED light represents cheaper, robust, and versatile alternative to traditional UV lamps. In this study, it was designed and evaluated a photoreactor with an approach of chemical fluid dynamics (CFD) and experimental validation. The evaluation consisted of (1) CFD velocity profile analysis, (2) characterization of the average light distribution with potassium ferrioxalate actinometry, (3) degradation of a typical recalcitrant metallic cyanocomplex Fe(CN)₆³⁻, and (4) scavenger effect analysis in the photodegradation using potassium persulfate. Actinometrical essay concluded that the system was able to receive 1.93 μE/s. The reactor operated under turbulent regime and best result for Fe(CN)₆³⁻ degradation was obtained at 4 h of operation, using 5-W UV-A LEDs, with pH ~ 7 and 10 mM de S₂O₈²⁻. Baffled photoreactor demonstrated to be useful for this type of illumination and wastewater treatment.