High molecular weight paraffins are known to form gels of complex morphology at low temperatures due to the low solubility of these compounds in aromatic or naphthene-base oil solvents. The characteristics of these gels are strong functions of the shear and thermal histories of these samples. A model system of wax and oil was used to understand the gelation process of these mixtures. A significant depression in the gel point of a wax-oil sample was observed by either decreasing the cooling rate or increasing the steady shear stress. The wax-oil sample separates into two layers of different characteristics, a gel-like layer and a liquid-like layer, when sheared with a controlled-stress rheometer at high steady shear stresses and low cooling rates. The phase diagram of the model wax-oil system, obtained using a controlled-stress rheometer, was verified by analyzing the wax content of the incipient gel deposits formed on the wall of a flow loop. Based on the rheological measurements, a law has been suggested for the prediction of the wax content of the gel deposit on the laboratory flow loop walls. The wax content of the incipient gel formed on the wall of a field subsea pipeline was predicted to be much higher than that for the flow loop at similar operating conditions. This variation in the gel deposit characteristics is due to the significant differences in the cooling histories in the two cases.
Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may impact clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy-associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803 mg) and the median duration of corticosteroid treatment was 9 days (range 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% CI 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible, while managing CAR T-cell therapy-associated toxicities.
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