Microwave assisted synthesis of dihydrobenzo [4,5]imidazo [1,2-a] pyrimidin-4-ones; synthesis, in vitro antimicrobial and anticancer activities of novel coumarin substituted dihydrobenzo [4,5] In general, all the compounds possessed better antifungal properties than antibacterial properties. The coumarin substituted dihydrobenzo [4,5]imidazo[1,2-a]pyrimidin-4-one (4g) (R ¼ i-Pr, R 1 ¼ 6-Cl) was found to be the most potent cytotoxic compound (88%) against Dalton's Ascitic Lymphoma cell line at the concentration of 100 mg/mL.
Background
Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome.
Methods
We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n = 127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n = 123) managed at one center during 2015–2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs).
Results
Sequential RTX therapy, initiated at a median of 10 years [interquartile range (IQR) 7.3–14.4], was administered for 1.8 courses/person-year [95% confidence interval (CI) 1.7–2.0] over 2.0 years (95% CI 1.2–3.0). Therapy was associated with postponement of relapses by a median of 3 years in patients with steroid-sensitive disease and 2 years in those with steroid resistance. Relapses were reduced by a mean of 2.0 relapses/person-year (95% CI 1.8–2.2), enabling a reduction in prednisolone dose to 0.04 mg/kg/day (95% CI 0.01–0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20 events/person-year (95% CI 0.17–0.23), were chiefly comprised of infusion reactions (n = 108) and infections (n = 46); serious adverse events were observed in 10.8% patients, at 0.03 events/person-year (95% CI 0.02–0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n = 52)] than tetanus [65.5% and 34.5% (n = 58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of <9–10 years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy.
Conclusions
Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions.
This paper deals with scalarization and stability aspects for a unified set optimization problem. We provide characterizations for a unified preference relation and the corresponding unified minimal solution in terms of a generalized oriented distance function of the sup-inf type. We establish continuity of a function associated with the generalized oriented distance function and provide an existence result for the unified minimal solution. We establish Painlevé-Kuratowski convergence of minimal solutions of a family of scalar problems to the minimal solutions of the unified set optimization problem.
the ORR was 54%. Of patients with Stage III/IV disease the median PFS was 5.7 months. Among those with paired biopsies, there was no change in H-score pSMAD after C1 in 3/4 patients with a partial response. 4 patients with paired samples had a decrease in epithelial component, this did not correlate with response. Conclusions GB was well tolerated with TC with no DLTs. Paired biopsies were too limited to make conclusions. However, the putative mechanism of action of galunisertib and the well tolerated nature of the combination would warrant further exploration.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.