Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis

Immunoglobulin light-chain amyloidosis (AL) and multiple myeloma (MM) are 2 distinct monoclonal gammopathies that involve the same cellular compartment: clonal plasma cells (PCs). Despite the fact that knowledge about MM PC biology has significantly increased in the last decade, the same does not apply for AL. Here, we used an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 24 newly diagnosed patients with AL. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and both monoclonal gammopathy of undetermined significance and MM PCs. However, in contrast to MM, highly purified fluorescence-activated cell-sorted clonal PCs from AL (n = 9) showed almost normal transcriptome, with only 38 deregulated genes vs normal PCs; these included a few tumor-suppressor (CDH1, RCAN) and proapoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n=11) were genomically unstable, with a median of 9 copy number alterations (CNAs) per case, many of such CNAs being similar to those found in MM. Whole-exome sequencing (WES) performed in 5 AL patients revealed a median of 15 nonrecurrent mutations per case. Altogether, our results show that in the absence of a unifying mutation by WES, clonal PCs in AL display phenotypic and CNA profiles similar to MM, but their transcriptome is remarkably similar to that of normal PCs

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

The spatial-temporal distribution of the atmospheric polluting agents during the period 2000-2005 in the Urban Area of Guadalajara, Jalisco, Mexico

In the large cities, the disordered urban development, the industrial activities, and the transport, have caused elevated concentrations of polluting agents and possible risks to the health of the population. The metropolises located in valleys with little ventilation (such as the Urban Area of Guadalajara: UAG) present low dispersion of polluting agents can cause high risk of respiratory and cardiovascular diseases. The objective of this work was to describe the spatial-temporal distribution of the atmospheric polluting agents: carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), particles smaller than 10 microns (?m) (PM10) and ozone (O3) in the UAG during the period 2000-2005. A spatial-temporal distribution analysis was made by means of graphic interpolation (Kriging method) of the statistical parameters of CO, NO2, SO2, PM10 and O3 with the collected data from eight stations of atmospheric monitoring in the UAG. The results show that the distributions of the atmospheric polluting agents are variable during the analyzed years. The polluting agent with highest concentration is PM10 (265.42 ?g/m3), followed by O3 (0.11 ppm), NO2 (0.11 ppm), CO (9.17 ppm) and SO2 (0.05 ppm). The most affected zone is the southeast of the UAG. The results showed that an important percentage of days exceed the Mexican norms of air quality (93-199 days/year). © 2008

Fluorescently labeled bevacizumab in human breast cancer: Defining the classification threshold.

In-vivo fluorescently labelled drug (bevacizumab) breast cancer specimen where obtained from patients. We propose a new structured method to determine the optimal classification threshold in targeted fluorescence intra-operative imaging