Acute kidney injury in villous cancer patients treated with vancomycin and tazobactam/piperacillin.

In this report, we present a 37-year-old woman with villous cancer who developed AKI after co-administration of VCM and TAZ/PIPC. Trough concentration of VCM reach a toxic level. Finally, she recovered on day 17.

KRAS and EGFR Amplifications Mediate Resistance to Rociletinib and Osimertinib in Acquired Afatinib-Resistant NSCLC Harboring Exon 19 Deletion/T790M in EGFR.

The critical T790M mutation in EGFR, which mediates resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKI; gefitinib, erlotinib, and afatinib), has facilitated the development of third-generation mutation-selective EGFR TKIs (rociletinib and osimertinib). We previously reported heterogeneous afatinib-resistant mechanisms, including emergence of T790M-EGFR, and responses to third-generation EGFR TKIs. Here, we used afatinib-resistant lung adenocarcinoma cells [AfaR (formerly AFR3) cells], carrying exon 19 deletion/T790M in EGFR To identify the novel resistance mechanisms in post-afatinib treatment, RocR1/RocR2 and OsiR1/OsiR2 cells were established using increasing concentrations of rociletinib and osimertinib, respectively. Attenuation of exon 19 deletion and T790M was confirmed in both rociletinib-resistant cells; in addition, EGFR and KRAS amplification was observed in RocR1 and RocR2, respectively. Significant KRAS amplification was observed in the osimertinib-resistant cell lines, indicating a linear and reversible increase with increased osimertinib concentrations in OsiR1 and OsiR2 cells. OsiR1 cells maintained osimertinib resistance with KRAS amplification after osimertinib withdrawal for 2 months. OsiR2 cells exhibited KRAS attenuation, and osimertinib sensitivity was entirely recovered. Phospho-EGFR (Y1068) and growth factor receptor-bound protein 2 (GRB2)/son of sevenless homolog 1 (SOS1) complex was found to mediate osimertinib resistance in OsiR1 cells with sustained KRAS activation. After 2 months of osimertinib withdrawal, this complex was dissociated, and the EGFR signal, but not the GRB2/SOS1 signal, was activated. Concomitant inhibition of MAPK kinase and EGFR could overcome osimertinib resistance. Thus, we identified a heterogeneous acquired resistance mechanism for third-generation EGFR TKIs, providing insights into the development of novel treatment strategies.

Drug-induced generalized skin eruption in a diabetes mellitus patient receiving a dipeptidyl peptidase-4 inhibitor plus metformin.

A generalized skin eruption with strong itching was induced by sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in a patient almost 6 months after initiation of the drug. Physical examination revealed a spread of skin rash from chest to back, and abdomen and thigh. Discontinuation of the drug eliminated the skin rash immediately. The emergence of new rash ended, and the rash itself withered after 1 week. The spread of the rash gradually shrank and the skin lesions subsided, leaving pigmentation 1 month later. Two months after cessation of sitagliptin, the skin eruption had subsided and oral steroid medication was stopped, but some small eczematous eruptions continued to appear intermittently. Although a drug-induced lymphocyte stimulation test was negative for sitagliptin, nonspecific radioimmunosorbent test for immunoglobulin E was increased to 532 IU/mL, with a percentage of eosinophil of 7.4%. Sitagliptin has a phenyl ring, carbonyl group, and an absorption spectrum showing three absorption peaks (199.9, 265.0, 400.1 nm), and its photosensitive mechanism could have been responsible for the itchy edematous plaque. In the present case, the initial generalized skin eruption may have been induced by an allergic reaction to sitagliptin. Close attention should be paid to patients receiving this drug with a history of urticaria, and to the development of photosensitivity.

[Factors influencing parental medication adherence in pediatric asthma].

PURPOSE: To identify the factors influencing parental medication control behaviors (inhaling corticosteroids and medication-taking) in pediatric asthma management. METHODS: A specially-designed questionnaire survey was conducted on 942 parents with asthmatic children in hospitals and elementary schools. RESULTS: Factor analysis on inhalation behaviors resulted in five factors: understanding of benefit, mastering on inhalation skills and medication management, family support, anxiety of side effects, and explanation from a doctor (cumulative contribution ratio=51.3%). Factor analysis on medication-taking behavior resulted in five factors: understanding of medication effectiveness and benefit, family support, anxiety of side effects, skills on giving medicines, and family routine (cumulative contribution ratio=50.6%). CONCLUSION: The results indicate the importance of recognizing factors influencing parental medication control behaviors in developing education strategies to maintain and reinforce their asthma management behaviors.