High risk of thrombosis in patients with advanced lung cancer harboring rearrangements in ROS1.

INTRODUCTION: Based on the high incidence of thromboembolic events (TEs) observed in lung adenocarcinomas with ALK translocations and taking into account the biological proximity of ROS1 and ALK, we conducted a retrospective analysis of patients with advanced lung carcinoma carrying rearrangements in ROS1 from 23 centres in Spain and one centre in Portugal. METHODS: The main objective of the study was to analyse the incidence of TE in this population, looking for predictive risk factors, and its impact on overall survival. RESULTS: A total of 58 patients were included. The incidence of TEs throughout the disease was 46.6% (n = 27) with a median follow-up of 19 months (range: 1-78 months) and a median overall survival of 52 months in the total population and 50 months for the patients presenting TEs, with a hazards ratio of 1.12 (95% confidence interval: 0.47-2.65) p = 0.78. The majority of the events were venous (n = 24; 89%) and occurred in the ambulatory setting (n = 18; 67%). Almost half of the patients (n = 13; 48%) presented the TE in the peri-diagnostic period. CONCLUSIONS: The high incidence of thrombosis, especially during the cancer diagnosis process, requires special attention from a clinician. Despite the limitations of such a small descriptive study, its results are in accordance with previously reported data. It would be important to design prospective studies of antithrombotic prophylaxis in this population because of their possible impact in reducing the risk of TEs.

Second-line treatment in advanced gastric cancer: Data from the Spanish AGAMENON registry.

BACKGROUND: Second-line treatments boost overall survival in advanced gastric cancer (AGC). However, there is a paucity of information as to patterns of use and the results achieved in actual clinical practice. MATERIALS AND METHODS: The study population comprised patients with AGC in the AGAMENON registry who had received second-line. The objective was to describe the pattern of second-line therapies administered, progression-free survival following second-line (PFS-2), and post-progression survival since first-line (PPS). RESULTS: 2311 cases with 2066 progression events since first-line (89.3%) were recorded; 245 (10.6%) patients died during first-line treatment and 1326/2066 (64.1%) received a second-line. Median PFS-2 and PPS were 3.1 (95% CI, 2.9-3.3) and 5.8 months (5.5-6.3), respectively. The most widely used strategies were monoCT (56.9%), polyCT (15.0%), ramucirumab+CT (12.6%), platinum-reintroduction (8.3%), trastuzumab+CT (6.1%), and ramucirumab (1.1%). PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months. Correlation between PFS since first-line and OS was moderate in the series as a whole (Kendall's τ = 0.613), lower in those subjects who received second-line (Kendall's τ = 0.539), especially with ramucirumab+CT (Kendall's τ = 0.413). CONCLUSION: This analysis reveals the diversity in second-line treatment for AGC, highlighting the effectiveness of paclitaxel-ramucirumab and, for a selected subgroup of patients, platinum reintroduction; both strategies endorsed by recent clinical guidelines.

Gas chromatography with mass spectrometry for the determination of phthalates preconcentrated by microextraction based on an ionic liquid.

A new procedure is proposed for the analysis of migration test solutions obtained from plastic bottles used in the packaging of edible oils. Ultrasound-assisted emulsification microextraction with ionic liquids was applied for the preconcentration of six phthalate esters: dimethylphthalate, diethylphthalate, di-n-butylphthalate, n-butylbenzylphthalate, di-2-ethylhexylphthalate, and di-n-octylphthalate. The enriched ionic liquid was directly analyzed by gas chromatography and mass spectrometry using direct insert microvial thermal desorption. The different factors affecting the microextraction efficiency, such as volume of the extracting phase (30 µL of the ionic liquid) and ultrasound application time (25 s), and the thermal desorption step, such as desorption temperature and time, and gas flow rate, were studied. Under the selected conditions, detection limits for the analytes were in the 0.012-0.18 µg/L range, while recovery assays provided values ranging from 80 to 112%. The use of butyl benzoate as internal standard increased the reproducibility of the analytical procedure. When the release of the six phthalate esters from the tested plastic bottles to liquid simulants was monitored using the optimized procedure, analyte concentrations of between 1.0 and 273 µg/L were detected.

Determination of synthetic phenolic antioxidants in edible oils using microvial insert large volume injection gas-chromatography.

Three synthetic phenolic antioxidants, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and tert-butyl hydroquinone (TBHQ), were determined in different edible vegetable oil samples. The analyses were carried out by gas chromatography-mass spectrometry (GC-MS) using microvial insert large volume injection (LVI). Several parameters affecting this sample introduction step, such as temperatures, times and gas flows, were optimised. Quantification was carried out by the matrix-matched calibration method using carvacrol as internal standard, providing quantification limits between 0.08 and 0.10 ng g(-1), depending on the compound. The three phenolic compounds were detected in several of the samples, BHT being the most frequently found. Recovery assays for oil samples spiked at two concentration levels, 2.5 and 10 ng g(-1), provided recoveries in the 86-115% range.

In situ ionic liquid dispersive liquid-liquid microextraction and direct microvial insert thermal desorption for gas chromatographic determination of bisphenol compounds.

A new procedure based on direct insert microvial thermal desorption injection allows the direct analysis of ionic liquid extracts by gas chromatography and mass spectrometry (GC-MS). For this purpose, an in situ ionic liquid dispersive liquid-liquid microextraction (in situ IL DLLME) has been developed for the quantification of bisphenol A (BPA), bisphenol Z (BPZ) and bisphenol F (BPF). Different parameters affecting the extraction efficiency of the microextraction technique and the thermal desorption step were studied. The optimized procedure, determining the analytes as acetyl derivatives, provided detection limits of 26, 18 and 19 ng L(-1) for BPA, BPZ and BPF, respectively. The release of the three analytes from plastic containers was monitored using this newly developed analytical method. Analysis of the migration test solutions for 15 different plastic containers in daily use identified the presence of the analytes at concentrations ranging between 0.07 and 37 µg L(-1) in six of the samples studied, BPA being the most commonly found and at higher concentrations than the other analytes.

Improved sensitivity gas chromatography-mass spectrometry determination of parabens in waters using ionic liquids.

A new procedure for the introduction of ionic liquid samples in gas chromatography (GC) is proposed. This procedure, based on microvial insert thermal desorption, allows the direct analysis of the compounds preconcentrated by ionic liquid based liquid-liquid microextraction (IL-LLME) using the combination of a thermal desorption unit (TDU) and a programmed temperature vaporization injector (PTV). Two different IL-LLME methodologies, one based on the formation of a microdroplet emulsion by dispersive liquid-liquid microextraction (DLLME) and other through ultrasound-assisted emulsification microextraction (USAEME) were studied and evaluated. IL-DLLME proved advantageous and consequently, it was adopted for preconcentration purposes. This easy to apply approach was used for the determination of five parabens (methyl-, ethyl-, propyl-, butyl- and isobutyl paraben) in swimming pool waters, after in situ acetylation. The optimized conditions of TDU/PTV allowed the analytes contained in 20 µL of the enriched IL to be transferred to the capillary column. Quantification of the samples was carried out against aqueous standards, and quantification limits of between 4.3 and 8.1 ng L(-1) were obtained, depending on the compound. Concentrations of between 9 and 47 ng L(-1) for some analytes were obtained in the analysis of ten samples.

Evaluation of the contamination of spirits by polycyclic aromatic hydrocarbons using ultrasound-assisted emulsification microextraction coupled to gas chromatography-mass spectrometry.

The concentration of twelve polycyclic aromatic hydrocarbons (PAHs), included in the list of priority pollutants, in different spirits has been obtained by means of a rapid and sensitive method based on gas chromatography and mass spectrometry (GC-MS). The environmentally friendly ultrasound-assisted emulsification microextraction (USAEME) technique allowed the easy and effective preconcentration of the PAHs from the sample matrices. Several parameters affecting the extraction efficiency, such as the nature and volume of the extractant solvent, and the addition of salt, as well as the sonication parameters were investigated and optimized. The absence of matrix effects under the optimized conditions allowed the sample quantification against aqueous standards. Detection limits ranged between 1.8 and 6.3 ng L(-1), depending on the compound. Different spirit samples were successfully analyzed using the proposed method, and contents of up to 0.9 µg L(-1) were found. Relative recoveries at fortified levels of 0.2 and 1 µg L(-1) were in the range 84-118%.

Changes in analytical and volatile compositions of red wines induced by pre-fermentation heat treatment of grapes.

Experiments were carried out on Grenache, Carignan and Fer grapes in order to characterize the changes in nitrogen content of the musts, conventional enological parameters and aroma compounds of the wines induced by pre-fermentation heating of the grapes followed by alcoholic fermentation in liquid phase or in solid phase. In comparison to a standard vinification, we showed that a two-hour heat treatment at 70 °C induced a significant loss in several grape-derived aroma compounds (terpenols, norisoprenoids and some phenols) associated with an increase in α-terpineol, guaiacol and 2,6-dimethoxyphenol, which suggests thermal degradation. A significant increase in most of the ethyl esters, in acetates and in fatty acids were observed in wines fermented in liquid phase, together with a decrease in fusel alcohols. The substantial modification in the amino acid composition of the must seems to be a crucial element for the understanding of these changes.

Determination of synthetic phenolic antioxidants in soft drinks by stir-bar sorptive extraction coupled to gas chromatography-mass spectrometry.

The synthetic phenolic antioxidants butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and tert-butyl hydroquinone (TBHQ) were pre-concentrated by stir-bar sorptive extraction and thermally desorbed (SBSE-TD) before analysis by GC-MS. Several parameters affecting the derivatisation step and both SBSE extraction and thermal desorption were carefully optimised. When the analyses of BHA and TBHQ in their acetylated, silylated and underivatised forms were compared, the best results were obtained when the in-situ derivatisation procedure with acetic anhydride was employed. Quantification was carried out using carvacrol as the internal standard, providing quantification limits of between 0.11 and 0.15 ng ml(-1), depending on the compound. Recovery assays for samples spiked at two concentration levels, 1 and 5 ng ml(-1), provided recoveries in the 81-117% range. The proposed method was applied in the analysis canned soft drinks and the analytes were found in five of the 10 samples analysed.

Influence of viticulture practices on grape aroma precursors and their relation with wine aroma.

BACKGROUND: The effects of two different operations in the vineyard (basal leaf plucking and head trimming) on the synthesis of aromatic precursors in the grape and their impact on wine aroma have been studied and compared with a control sample. The study was carried out over two consecutive years with four different varieties. Glycosidic precursors were analysed in grapes and volatile compounds were studied in the wines. ANOVA studies were performed to study the effect of the vintage, variety and treatment for each of the compounds released from their precursors. RESULTS: Regarding treatment, the highest values in the concentration of free aroma compounds were achieved in the leaf plucking grapes, except for Chardonnay. Significant and positive correlations between aromatic precursors of terpenes present in grapes and their released form in wines were found for all varieties. For norisoprenoids, significant and positive correlations were exclusively found for Chardonnay and for phenols and vanillins in the year 2010 the correlations were high in three of the four varieties studied. CONCLUSION: In the assays of the 2 years, more precursors were synthesised in Merlot, Gewurztraminer and Tempranillo grapes if the vineyards were plucked.

A model explaining and predicting lamb flavour from the aroma-active chemical compounds released upon grilling light lamb loins.

The objective of the work is to understand the role of the different aroma compounds in the perception of the local "lamb flavour" concept. For this, a set of 70 loins (Longissimus dorsi) from approximately seventy day-old Rasa Aragonesa male lambs were grilled and the aroma-active chemicals released during the grilling process were trapped and analyzed. Carbonyl compounds were derivatizated and determined by GC-NCI-MS, whereas other aromatic compounds were directly analyzed by GC-GC-MS. Odour activity values (OAVs) were calculated using their odour threshold values in air. Lamb flavour could be satisfactory explained by a partial least-squares model (74% explained variance in cross-validation) built by the OAVs of 32 aroma-active chemical compounds. The model demonstrates that the lamb flavour concept is the result of a complex balance. Its intensity critically and positively depends to the levels of volatile fatty acids and several dimethylpyrazines while is negatively influenced by the different alkenals and alkadienals. (E,E)-2,4-decadienal and (E)-2-nonenal showed top OAVs.

Comparative analysis of aroma compounds and sensorial features of strawberry and lemon guavas (Psidium cattleianum Sabine).

The aroma of strawberry and lemon guava fruits (Psidium cattleianum Sabine) was studied by sensory analysis, gas chromatography-olfactometry (GC-O) and quantitative analysis. Volatiles released from the pulps were collected in a trapping system consisting of LiChrolut EN resins and eluted with dichloromethane/methanol. In total, 23 odour zones were detected by GC-O, of which 16 were found in the extract from the strawberry guava pulp and 17 in the extract from the lemon guava pulp. Among the compounds identified, only 10 were common to both strawberry and lemon guavas. The descriptive sensorial analysis differentiated between the aroma profiles of the strawberry guava pulp with the descriptor "tomato" and the lemon guava pulp with the descriptor "tropical fruit". The typical aroma of the guava fruits was dominated by the presence of numerous aldehydes and ketones among which (Z)-3-hexenal was the most intense odorant, while 1,8-cineole and linalool were also revealed as important aroma constituents.

Volatile profile of Madeira wines submitted to traditional accelerated ageing.

The evolution of monovarietal fortified Madeira wines forced-aged by traditional thermal processing (estufagem) were studied in terms of volatiles. SPE extracts were analysed by GC-MS before and after heating at 45 °C for 3 months (standard) and at 70 °C for 1 month (overheating). One hundred and ninety volatile compounds were identified, 53 of which were only encountered in baked wines. Most chemical families increased after standard heating, especially furans and esters, up to 61 and 3-fold, respectively. On the contrary, alcohols, acetates and fatty acids decreased after heating. Varietal aromas, such as Malvasia's monoterpenic alcohols were not detected after baking. The accelerated ageing favoured the development of some volatiles previously reported as typical aromas of finest Madeira wines, particularly phenylacetaldeyde, ß-damascenone and 5-ethoxymethylfurfural. Additionally, ethyl butyrate, ethyl 2-methylbutyrate, ethyl caproate, ethyl isovalerate, guaiacol, 5-hydroxymethylfurfural and γ-decalactone were also found as potential contributors to the global aroma of baked wines.

Stir bar sorptive extraction polar coatings for the determination of chlorophenols and chloroanisoles in wines using gas chromatography and mass spectrometry.

The simultaneous determination of 14 chlorophenols (CPs) and chloroanisoles (CAs) in wine samples is carried out using stir bar sorptive extraction (SBSE) with thermal desorption and gas chromatography-mass spectrometry (TD-GC-MS), evaluating the preconcentration efficiency of two different polar extracting phases, ethylene glycol-silicone (EG-Silicone) copolymer and polyacrylate, which have recently become commercially marketed. The influence of several extraction variables on the preconcentration capacity of these two novel coatings was tested, as well as the variables affecting the thermal desorption step. The EG-Silicone extraction phase provided the best results, since it allowed the simultaneous preconcentration of both species the non-polar CAs, due to the silicone base, and the polar CPs, because of the ethylene glycol polymer. Consequently, under the finally selected conditions, CPs were determined without any derivatization step, reaching detection limits in the 0.3-1.4 ng L(-1) range, depending on the compound. For CAs the detection limits ranged from 0.2 to 0.5 ng L(-1), with good precision and recovery. Five CAs and three CPs were found in several analyzed wines, some of which can be regarded as defective considering their contents in 2,4,6-TCA and 2,6-DCA.

Polyphenols, antioxidant potential and color of fortified wines during accelerated ageing: the Madeira Wine case study.

Polyphenols, antioxidant potential and color of three types of fortified Madeira wines were evaluated during the accelerated ageing, named as estufagem. The traditional estufagem process was set to 45 °C for 3 months. Overheating conditions, 1 month at 70 °C, were also examined. Total polyphenols (TP), total monomeric anthocyanins (TMA) and total flavonoids (TF) were assessed by spectrophotometric methods, while individual polyphenols and furans were simultaneously determined by HPLC-DAD. Antioxidant potential (AP) was estimated by ABTS, DPPH and FRAP assays, while color was evaluated by Glories and CIELab. Traditional estufagem decreased the TP and AP up to 20% and 26%, respectively, with final values similar to other wines. TMA of the Madeira wines from red grapes decreased during estufagem. Six hydroxybenzoic acids, three hydroxycinnamic acids, one stilbene, three flavonols and three flavan-3-ols were found in these wines. The prominent phenolics were hydroxycinnamates and hydroxybenzoates, even after estufagem. Most polyphenols decreased, with the exception of caffeic, ferulic, p-coumaric, gallic and syringic acids. Finally, both chromatic systems revealed that all wines tended to similar chromatic characteristics after estufagem. The study suggests that estufagem can be applied without high impact on polyphenols and antioxidant potential of these fortified wines.

Stir bar sorptive extraction with EG-Silicone coating for bisphenols determination in personal care products by GC-MS.

An easy to perform analytical method for the determination of three bisphenol compounds (BPs) in commonly used personal care products (PCPs) is presented. Ethylene glycol-silicone (EG-Silicone) coated stir bars, which have recently become commercially available, are evaluated in this study for the simultaneous determination of bisphenol A (BPA), bisphenol F (BPF) and bisphenol Z (BPZ) by stir bar sorptive extraction (SBSE) in combination with thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). This new sorptive extraction phase allows the analysis of these compounds without any previous derivatization procedure. Different parameters affecting both SBSE extraction and thermal desorption were carefully optimized, using experimental designs based on the Taguchi orthogonal arrays. The procedure was applied to analyzing easily bought PCPs, providing detection limits of about 8 ng g(-1), with precisions lower than 11% in terms of relative standard deviation. Recovery studies performed at two different concentration levels provided satisfactory values for all the compounds. The analyzed personal care samples contained BPA at concentration levels ranging from 30.9 to 88.3 ng g(-1).

3-Methyl-2-butene-1-thiol: identification, analysis, occurrence and sensory role of an uncommon thiol in wine.

A highly uncommon odorant, 3-methyl-2-butene-1-thiol was detected by using Gas Chromatography-Olfactometry (GC-O) and unequivocally identified for the first time in wine. A purge and trap sampling technique which provides highly representative extracts for olfactometric analysis was used for the extraction of the volatile fraction of a Spanish red wine made from Prieto Picudo grapes. The identification of the odorant was achieved by multidimensional gas chromatography analysis of the same purge and trap extract. Mass spectrum and retention indices in both polar and non-polar columns allowed knowing unequivocally the identity. To obtain quantitative data a method was validated for the analysis of the compound at ng L(-1) level with acceptable precision. This powerful odorant presented an odor threshold in wine of 0.5-1 ng L(-1) and it has been detected in several Prieto Picudo wines at concentrations slightly above the odor threshold.

Aroma chemical composition of red wines from different price categories and its relationship to quality.

The aroma chemical composition of three sets of Spanish red wines belonging to three different price categories was studied by using an array of gas chromatographic methods. Significant differences were found in the levels of 72 aroma compounds. Expensive wines are richest in wood-related compounds, ethyl phenols, cysteinil-derived mercaptans, volatile sulfur compounds, ethyl esters of branched acids, methional, and phenylacetaldehyde and are poorest in linear and branched fatty acids, fusel alcohols, terpenols, norisoprenoids, fusel alcohol acetates, and ethyl esters of the linear fatty acids; inexpensive wines show exactly the opposite profile, being richest in E-2-nonenal, E-2-hexenal, Z-3-hexenol, acetoin, and ethyl lactate. Satisfactory models relating quality to odorant composition could be built exclusively for expensive and medium-price wines but not for the lower-price sample set in which in-mouth attributes had to be included. The models for quality reveal a common structure, but they are characteristic of a given sample set.

Quality and aromatic sensory descriptors (mainly fresh and dry fruit character) of Spanish red wines can be predicted from their aroma-active chemical composition.

A satisfactory model explaining quality could be built in a set of 25 high quality Spanish red wines, by aroma-active chemical composition. The quality of the wines was positively correlated with the wine content in fruity esters, acids, enolones, and wood derived compounds, and negatively with phenylacetaldehyde, acetic acid, methional, and 4-ethylphenol. Wine fruitiness was demonstrated to be positively related not only to the wine content on fruity esters and enolones, but to wine volatile fatty acids. Fruitiness is strongly suppressed by 4-ethylphenol, acetic acid, phenylacetaldehyde, and methional, this involved in the perception of dry-fruit notes. Sensory effects were more intense in the presence of ß-damascenone and ß-ionone. A satisfactory model explaining animal notes could be built. Finally, the vegetal character of this set of wines could be related to the combined effect of dimethylsulfide (DMS), 1-hexanol, and methanethiol.

Analytical and sensorial characterization of the aroma of wines produced with sour rotten grapes using GC-O and GC-MS: identification of key aroma compounds.

In the present work, the aroma profiles of wines elaborated from sound and sour rot-infected grapes as raw material have been studied by sensory analysis, gas chromatography-olfactometry (GC-O), and gas chromatography-mass spectrometry (GC-MS), with the aim of determining the odor volatiles most likely associated with this disease. The effect of sour rot was tested in monovarietal wines produced with the Portuguese red grape variety Trincadeira and in blends of Cabernet Sauvignon and sour rotten Trincadeira grapes. Wines produced from damaged berries exhibited clear honey-like notes not evoked by healthy samples. Ethyl phenylacetate (EPhA) and phenylacetic acid (PAA), both exhibiting sweet honey-like aromas, emerged as key aroma compounds of sour rotten wines. Their levels were 1 order of magnitude above those found in controls and reached 304 and 1668 µg L(-1) of EPhA and PAA, respectively, well above the corresponding odor thresholds. Levels of γ-nonalactone also increased by a factor 3 in sour rot samples. Results also suggest that sour rot exerts a great effect on the secondary metabolism of yeast, decreasing the levels of volatiles related to fatty acids and amino acid synthesis. The highest levels of γ-decalactone of up to 405 µg L(-1) were also found in all of the samples, suggesting that this could be a relevant aroma compound in Trincadeira wine aroma.