Predictive Value of Tumor Ki-67 Expression in Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer

Several small studies have reported that having a high percentage of breast tumor cells that express the proliferation antigen Ki-67 (ie, a high Ki-67 labeling index) predicts better response to neoadjuvant chemotherapy. However, the predictive value of a high Ki-67 labeling index for response to adjuvant chemotherapy is unclear. To investigate whether Ki-67 labeling index predicts response to adjuvant chemoendocrine therapy, we assessed Ki-67 expression in tumor tissue from 1924 (70%) of 2732 patients who were enrolled in two randomized International Breast Cancer Study Group trials of adjuvant chemoendocrine therapy vs endocrine therapy alone for node-negative breast cancer. A high Ki-67 labeling index was associated with other factors that predict poor prognosis. Among the 1521 patients with endocrine-responsive tumors, a high Ki-67 labeling index was associated with worse disease-free survival but the Ki-67 labeling index did not predict the relative efficacy of chemoendocrine therapy compared with endocrine therapy alone. Thus, Ki-67 labeling index was an independent prognostic factor but was not predictive of better response to adjuvant chemotherapy in these studie

Reversed-phase and weak anion-exchange mixed-mode stationary phase for fast separation of medium-, long- and very long chain free fatty acids by ultra-high- performance liquid chromatography-high resolution mass spectrometry

Two commercial stationary phases allowing both reversed phase mechanism and anion-exchange with different selectivity, i.e. CSH C18 and Atlantis PREMIER BEH C18 AX, were tested for the separation of a complex mixture of 21 fatty acids (FAs) encompassing saturated medium-, long- and very long chain FAs, unsaturated long and very long chain FAs, cis/trans isomers, and isomers of odd- and branched-chain FAs. For this purpose, the role of surface area of stationary phase and the effect of pH of the mobile phase on the retention of the analytes were investigated. Separation was performed by ultra-high-performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS). BEH C18 AX was shown to be more versatile and to offer superior retention of these analytes to CSH C18 owing to a higher surface area and anion-exchange capacity up to pH 8.5. The UHPLC system allows shortening analysis time, the chromatographic analysis being accomplished in about 5 min, affording a high throughput of samples without the need for derivatization or ion-pairing reagents compared to techniques based upon gas chromatography approaches or LC. Finally, the application of the BEH C18 AX column using UHPLC-HRMS was demonstrated for the separation and unambiguous identification of FAs of nutritional interest in a dietary supplement sample

Optimization of the solid phase microextraction procedure for the ultra-trace determination of organotin compounds by gas chromatography-inductively coupled plasma-mass spectrometry

A chemometric approach based on experimental design and desirability functions was used to develop and validate a SPME-GC-ICP-MS method for the determination of the organotin compounds dimethyltin, tributyltin and dibuthyltin. Three different SPME coatings were evaluated, obtaining the best results by using the divinylbenzene/carboxen/polydimethylsiloxane 2 cm 50/30 mm fibre. The optimal extraction conditions were found to be the following: T ¼ 30 1C, t ¼ 40 min and pH ¼ 4. Method validation was performed by determining the most relevant quality parameters such as detection limit, quantitation limit, repeatability and intermediate precision. LOD values in the 0.2–8 ng L_1 were obtained

Use of experimental design for optimisation of the cold plasma ICP-MS determination of lithium, aluminum and iron in soft drinks and alcoholic beverages

A sensitive method for the simultaneous determination of Li-7, Al-27 and Fe-56 by cold plasma ICP-MS was developed and validated. Experimental design was used to investigate the effects of torch position, torch power, lens 2 voltage, and coolant flow. Regression models and desirability functions were applied to find the experimental conditions providing the highest global sensitivity in a multi-elemental analysis. Validation was performed in terms of limits of detection (LOD), limits of quantitation (LOQ), linearity and precision. LODs were 1.4 and 159 ng L-1 for Li-7 and Fe-56, respectively; the highest LOD found being that for Al-27 (425 ng L-1). Linear ranges of 5 orders of magnitude for Li and 3 orders for Fe were statistically verified for each compound. Precision was evaluated by testing two concentration levels, and good results in terms of both intra-day repeatability and intermediate precision were obtained. RSD values lower than 4.8% at the lowest concentration level were calculated for intra-day repeatability. Commercially available soft drinks and alcoholic beverages contained in different packaging materials (TetraPack(R), polyethylene terephthalate (PET), commercial cans and glass) were analysed, and all the analytes were detected and quantitated

Development and validation of an inductively coupled plasma mass spectrometry method with optimized microwave-assisted sample digestion for the determination of platinum at ultratrace levels in plasma and ultrafiltrate plasma

A highly sensitive inductively coupled plasma-mass spectrometry (ICP-MS) method with microwave-assisted sample digestion for the determination of total platinum in rat whole and ultrafiltrate plasma was developed and validated. A first step of this study concerned the optimization of the mineralization procedure, in order to obtain good extraction recovery (higher than 90%) and repeatability (less than 6%) and the absence of matrix effect. ICP-MS analysis was then performed using the “hot plasma/protective ion extraction” mode, achieving high sensitivity and very high signal/noise ratio. Iridium was added as internal standard. The method was then submitted to validation, performed according to the FDA Bioanalytical Validation Methods guidelines and to the Eurachem guide. Validation was carried out in terms of limit of detection (LOD), limit of quantitation (LOQ), linearity, precision, accuracy and stability. An instrumental LOQ of 1.9 ng L-1, corresponding to a concentration of 955 ng L-1 in matrix under the adopted conditions, was obtained, allowing the quantitative analysis of Pt ultratraces. Instrumental linearity was verified in the range 1.9-14000 ng L-1, corresponding to a concentration range from 955 ng L-1 to 6825 μg L-1 in matrix. Accuracy was evaluated by analyzing control samples for both matrices at different concentration levels; a good agreement (<15%) was obtained. Sample stability was tested by analyzing control samples maintained for 4 hours at room temperature or submitted to three freezing-thawing cycles. Finally, the developed method was applied to the analysis of plasma and ultrafiltrate plasma of rats treated with oxaliplatin-base drug, thus demonstrating its reliability in pharmacokinetic studies

ESEM-EDS-based analytical approach to assess nanoparticles for food safety and environmental control

Particulate contamination in the form of nanoparticles (NPs) can occur not only in the environment but also in the food production chain, making human exposure almost inevitable. In the present study the potentialities of Environmental Scanning Electron Microscopy coupled with Energy-Dispersive X-ray Spectroscopy (ESEM-EDS) were exploited for the detection and visualization of inorganic NPs in air, raw materials and food products along the pasta production chain (wheat ear, wheat, semolina and pasta). Investigation of the elemental composition of NPs in the same samples was also carried out by using two independent techniques: ESEM-EDS and Inductively Coupled Plasma Mass Spectrometry (ICP-MS). As for airborne particles, size-fractionated sampling was performed by an eight-stage cascade impactor located near the production plant with different exposition times for both ESEM-EDS and gravimetric analysis, respectively. In the case of raw materials and food products, the particles were collected on polycarbonate filters after immersion in milli-Q water in order to recover the NPs deriving from external environmental contamination. Only particle sizes lower than 0.8 µm were taken into consideration when ESEM-EDS analysis was carried out. NPs containing mainly Fe and Ti having dimensions &lt; 0.15 µm were identified in the filters used for wheat ear, wheat, semolina and pasta samples. As for air monitoring, gravimetric analysis showed an increase in the concentration levels of total particles during winter, particularly in the case of fine particulate matter (PM2.5). ESEM-EDS analysis, performed on filters of the VII and final stages, evidenced the same trend observed by gravimetric analysis, the majority of Fe-containing NPs being detected

Severe Typhoid Fever Complicated by Superior Mesenteric and Splenic Vein Thrombosis

Typhoid fever (Typhoid or enteric fever) is still the most common bacterial bloodstream infection worldwide, caused by Salmonella typhi. The transmission route is indirect through passive vehicles such as contaminated water or food. Main clinical findings are a fever lasting more than three days, abdominal symptoms, leukocytosis, and anemia. Typhoid can cause a wide range of multi-organ complications. We report a particularly severe form of this infection complicated by superior mesenteric vein and splenic vein thrombosis, an extremely uncommon manifestation

Development of a combined SEM and ICP-MS approach for the qualitative and quantitative analyses of metal nano- and microparticles in food products

Erratum to: Development of a combined SEM and ICP-MS approach for the qualitative and quantitative analyses of metal microparticles and sub-microparticles in food products published in Anal Bioanal Chem (2011) 401:1453 DOI 10.1007/s00216-011-5241-