Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study

Despite recent identification of several prognostic markers, there is still a need for new prognostic parameters able to predict clinical outcome in chronic lymphocytic leukemia (CLL) patients. Here, we aimed to validate the prognostic ability of known (proteomic) markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL. To this end, baseline serum samples of 51 CLL patients treated with chemo-immunotherapy were analyzed for 360 proteomic markers, using Olink technology. Median event-free survival (EFS) was 23 months (range: 1.25–60.9). Patients with high levels of sCD23 (>11.27, p = 0.026), sCD27 (>11.03, p = 0.04), SPINT1 (>1.6, p = 0.001), and LY9 (>8.22, p = 0.0003) had a shorter EFS than those with marker levels below the median. The effect of sCD23 on EFS differed between immunoglobulin heavy chain variable gene-mutated and unmutated patients, with the shortest EFS for unmutated CLL patients with sCD23 levels above the median. Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients

Occurrence of Penicillium verrucosum, ochratoxin A, ochratoxin B and citrinin in on-farm stored winter wheat from the Canadian Great Lakes Region

The occurrence of P. verrucosum and ochratoxin A (OTA) were surveyed for 3 and 4 years, respectively. A total of 250 samples was collected from an average of 30 farms during the 2011, 2012, 2013 and 2014 winter seasons. Most storage bins surveyed were typically 11 m high round bins made of corrugated, galvanized steel, with flat-bottoms and conical roofs. Samples of clumped grain contained the most P. verrucosum (p<0.05, n = 10) followed by samples taken from the first load (n = 24, mean = 147±87 CFU/g) and last load (n = 17, mean = 101±77 CFU/g). Five grain samples (2.2%) tested positive for OTA, citrinin and OTB at concentrations of 14.7±7.9, 4.9±1.9 and 1.2±0.7 ng/g, with only three samples exceeding 5 ng/g. Grain samples positive for OTA were related to moisture resulting from either condensation or migrating moist warm air in the bin or areas where precipitation including snow entered the bin. Bins containing grain and clumps contaminated with OTA were studied in detail. A number of statistically-significant risk factors for OTA contamination were identified. These included 1) grain clumps accumulated around or directly under manhole openings, 2) debris and residue of old grain or grain clumps collected from the bin walls or left on storage floor and augers and 3) grain clumps accumulated around side doors. Even when grain enters storage below the 14.5% threshold of moisture, condensation and moisture migration occurs in hotspots in modern corrugated steel storage bins. Hot spots of OTA contamination were most often in areas affected by moisture migration due to inadequate aeration and exposure to moisture from precipitation or condensation. Further, we found that the nature of the condensation affects the nature and distribution of small and isolated areas with high incidence of toxin contamination and/or P. verrucosum prevalence in the grain bins examined

Mycotoxins in fuel ethanol co-products derived from maize: A mass balance for deoxynivalenol

BACKGROUND: Three matrices - corn (maize) meal, distiller's dried grains with solubles (DDGS) and condensed distiller's solubles (CDS) - were sampled in sequence from a continuous dry-milling process plant for the determination of mass balance of deoxynivalenol (DON). Four commercially available enzyme-linked immunosorbent assay (ELISA) kits were evaluated for their ability to measure the presence of DON. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) was used as standard method to detect DON and other Fusarium toxins. Results: The concentrations of DON in DDGS and especially CDS were over estimated or under estimated by ELISA. However, for both matrices, all ELISA methods were not significantly different in their mean results from the LC/MS/MS standard, although the variability in results was much higher. DON concentrations in the CDS and the final DDGS co-product were significantly higher (P ≤ 0.01) than in the starting material (corn grain). Toxin concentration increased by a factor of 3 on a dry weight basis in DDGS compared with the starting corn and by a factor of 4 in CDS. Mean concentration of DON in CDS was four times higher (7.11 mg kg-1) than in corn grains (1.80 mg kg-1) and 1.4 times higher than in DDGS (5.24 mg kg-1). Mass balance calculations showed that CDS was the main source of contamination of DON, comprising ca 70% of the toxin found in the final product (DDGS). Most DON (87%) was accounted for by this analysis. CONCLUSION: Concentrations in the grain corn entering ethanol plants should be close to the dietary values recommended for swine in Canada and the USA for DON (1 mg kg-1). Small amounts of acetyldeoxynivalenol and DON glucoside were also found in the three matrices along with a small amount of zearalenone. Unlike the situation for DON, the DON glucoside was not concentrated into DDGS and CDS, indicating that it was hydrolysed during the fermentation process