Daratumumab plus lenalidomide and dexamethasone in relapsed/ refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse

An integrated method for the simultaneous determination of alkylphenol ethoxylates and brominated flame retardants in sewage sludge samples by ultrasonic-assisted extraction, solid phase clean-up, and GC-MS analysis

Generally, a major route of alkylphenol ethoxylates (APEs) and brominated flame retardants (BFRs) to enter the environment is via the wastewater treatment works (WWTW) facilities. Consequently, the levels of APEs and BFRs in sewage sludges may give an indication of the general use and exposure of these compounds. The present study was aimed at an integrated method for the analysis and quantification of APEs and BFRs in sewage sludge from selected wastewater treatment plants. The optimization of the extraction procedure included variation of the amount of extracted biomass, the duration, temperature during sonication as well as type of extraction solvent. Chromatographic determinations of APEs and BFRs were carried out with gas chromatography equipped with mass spectrometry detector after derivatization with heptafluorobutyric anhydride (HFBA). The mean percentage recoveries ranged from 39% to 79% (n = 3) for sewage sludge after extracting 5 g biomass sludge with hexane: acetone (4:1) at 55 °C for 45 min in two cycles. The mean concentrations of APEs obtained ranged from < LOQ to 365 ng g− 1, < LOQ to 166 ng g− 1, < LOQ to 642 ng g− 1 while the concentration of BFRs obtained range from < LOQ- 17 ng g− 1, < LOQ to 163 ng g− 1, < LOQ to 14 ng g− 1 for sludge samples from Leeuwkuil, Rietspruit, and Sebokeng, respectively. All compounds, except for nonylphenol (NP), BDE47, and BDE154, were detected from the Rietspruit WWTW. The presence of these pollutants in Rietspruit WWTW may be attributed by the fact that this treatment plants treat wastewater from domestic as well industrial discharges from the surrounding area

Occurrence and distribution pattern of alkylphenol ethoxylates and brominated flame retardants in sediment samples from Vaal River, South Africa.

High environmental concentrations for alkylphenol ethoxylates (APEs) and brominated flame retardants (BFRs) have been observed near cities than in rural environment. This is due, in part, to sewage systems receiving effluents from many industrial processes along with domestic wastewater. While these classes of compounds are being phased out in most developed countries, there is still widespread use in low to middle income countries. To better understand the extent of APEs and BFRs contamination in the environment, this study reports on the concentration and distribution of APEs and BFRs in sediments samples collected from Vaal River, South Africa. Measurable concentrations of these contaminants were obtained using GC–MS after heptafluorobutyric derivatization. The concentrations range (ng g−1) for these pollutants were as follows: nd–46, 20–127, 24–38, 3–5, 14–28, 16–54 for octylphenol penta ethoxylates, nonylphenol ethoxylates (mono- di), nonylphenol penta ethoxylates, PBB101, PBDEs, and HBCD; respectively. The distribution observed in this study indicated higher levels of sediment contamination by APEs relative to BFRs. These results underline the need to further investigate the burden and risks associated with chemical contamination in developing countries

Optimization and Simultaneous Determination of Alkyl Phenol Ethoxylates and Brominated Flame Retardants in Water after SPE and Heptafluorobutyric Anhydride Derivatization followed by GC/MS

A gas chromatography–mass spectrometry (GC–MS) method was investigated for the simultaneous analysis of two types of endocrine disrupting compounds (EDCs), i.e., alkylphenol ethoxylates and brominated flame retardants (BFRs), by extraction and derivatization followed by GC–MS. Different solid phase extraction (SPE) cartridges (Cleanert PestiCarb, C(18), Cleanert-SAX and Florosil), solvents (toluene, tetrahydrofuran, acetone, acetonitrile and ethyl acetate) and bases (NaHCO(3), triethylamine and pyridine) were tested and the best chromatographic analysis was achieved by extraction with Strata-X (33 μm, Reverse Phase) cartridge and derivatization with heptafluorobutyric anhydride at 55 °C under Na(2)CO(3) base in hexane. It was observed that APE together with lower substituted PBBs (PBB1, PBB10, PBB18 and PBB49), HBCD and TBBPA can be determined simultaneously under the same GC conditions. This simple and reliable analytical method was applied to determining trace amounts of these compounds from wastewater treatment plant samples. The recoveries of the target compounds from simulated water were above 60 %. The limit of detection ranged from 0.01 to 0.15 μg L(−1) and the limit of quantification ranged from 0.05 to 0.66 μg L(−1). There were no appreciable differences between filtered and unfiltered wastewater samples from Leeuwkil treatment plant although concentration of target analytes in filtered influent was slightly lower than the concentration of target analytes in unfiltered influent water. The concentrations of the target compounds from the wastewater treatment were determined from LOQ upwards

A simplified analytical procedure for simultaneous determination of alkylphenol ethoxylates and brominated flame retardants in fish tissue samples from Vaal River, South Africa.

In this study, the concentration of alkylphenol ethoxylates (APEs) and brominated flame retardants (BFRs) were determined in fish samples, Labeo umbratus and Carp, collected from the Vaal River in South Africa. Ultrasonic-assisted extraction technique was used to extract the organic contaminants from fish samples, and the resulting extract was purified by sulphuric acid lipid removal followed by Strata X-cartridge SPE clean-up. The APEs and BFRs were derivatized using heptafluorobutyric anhydride before analysis with GC-MS. In both types of fish samples, lower oligomers of APEs were more abundant than the higher oligomers, while HBCD, BDE99 and PBB101 were the dominant BFRs. The concentrations of these pollutants ranged from 1.061 ng/g lipids (t-BP) in Labeo umbratus to 11.860 ng/g lipids (HBCD) in Carp

Propensity of <i>Tagetes erecta</i> L., a Medicinal Plant Commonly Used in Diabetes Management, to Accumulate Perfluoroalkyl Substances

It has been extensively demonstrated that plants accumulate organic substances emanating from various sources, including soil and water. This fact suggests the potentiality of contamination of certain vital bioresources, such as medicinal plants, by persistent contaminants, such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorobutane sulfonate (PFBS). Hence, in this study, the propensity of Tagetes erecta L. (a commonly used medicinal plant) to accumulate PFOA, PFOS, and PFBS was determined using liquid chromatography/tandem mass spectrometry (LC&#8211;MS/MS-8030). From the results, PFOA, PFOS, and PFBS were detected in all the plant samples and concentration levels were found to be 94.83 ng/g, 5.03 ng/g, and 1.44 ng/g, respectively, with bioconcentration factor (BCF) ranges of 1.30 to 2.57, 13.67 to 72.33, and 0.16 to 0.31, respectively. Little evidence exists on the bioaccumulative susceptibility of medicinal plants to these persistent organic pollutants (POPs). These results suggest that these medicinal plants (in particular, Tagetes erecta L., used for the management of diabetes) are also potential conduits of PFOA, PFOS, and PFBS into humans

Propensity of tagetes erecta L., a medicinal plant commonly used in diabetes management, to accumulate perfluoroalkyl substances

Abstract: It has been extensively demonstrated that plants accumulate organic substances emanating from various sources, including soil and water. This fact suggests the potentiality of contamination of certain vital bioresources, such as medicinal plants, by persistent contaminants, such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorobutane sulfonate (PFBS). Hence, in this study, the propensity of Tagetes erecta L. (a commonly used medicinal plant) to accumulate PFOA, PFOS, and PFBS was determined using liquid chromatography/tandem mass spectrometry (LC–MS/MS-8030). From the results, PFOA, PFOS, and PFBS were detected in all the plant samples and concentration levels were found to be 94.83 ng/g, 5.03 ng/g, and 1.44 ng/g, respectively, with bioconcentration factor (BCF) ranges of 1.30 to 2.57, 13.67 to 72.33, and 0.16 to 0.31, respectively. Little evidence exists on the bioaccumulative susceptibility of medicinal plants to these persistent organic pollutants (POPs). These results suggest that these medicinal plants (in particular, Tagetes erecta L., used for the management of diabetes) are also potential conduits of PFOA, PFOS, and PFBS into humans

Memory awareness profiles differentiate mild cognitive impairment from early-stage dementia: evidence from assessments of performance monitoring and evaluative judgement

Background: Measures of memory awareness based on evaluative judgement and performance monitoring are often regarded as equivalent, but the Levels of Awareness framework suggests they reflect different awareness phenomena. Examination of memory awareness among groups with differing degrees of impairment provides a test of this proposition. Method: Ninety-nine people with dementia (PwD), 30 people with mild cognitive impairment (PwMCI), and their relatives completed isomorphic performance monitoring and evaluative judgement measures of memory awareness and were followed up at 12 and (PwD only) 20 months. In addition to the resulting awareness indices, comparative accuracy scores were calculated using the relatives’ data to establish whether any inaccuracy was specific to self-ratings. Results: When making evaluative judgements about their memory in general, both PwD and PwMCI tended to overestimate their own functioning relative to informant ratings made by relatives. When monitoring performance on memory tests, PwD again overestimated performance relative to test scores, but PwMCI were much more accurate. Comparative accuracy scores indicated that, unlike PwD, PwMCI do not show a specific inaccuracy in self-related appraisals. Conclusions: The results support the proposition that awareness indices at the levels of evaluative judgement and performance monitoring should be regarded as reflecting distinct awareness phenomena