With the widespread use of broad-spectrum antibiotics in clinical practice, the emergence of multidrug-resistant (MDR) gram-negative bacteria has become a global problem. The MDR Pseudomonas aeruginosa infection is especially difficult to treat and increases mortality in critically ill patients. Ceftolozane-tazobactam (Zerbaxa™) is a fifth-generation cephalosporin and beta-lactamase inhibitor that has proved to be effective for treating complicated urinary tract infections and complicated intra-abdominal infections caused by MDR P. aeruginosa. Herein, we report the first case of pediatric hematologic cancer in Korea that was successfully treated for MDR P. aeruginosa bacteremia with Ceftolozane-tazobactam.

PURPOSE: Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors. MATERIALS AND METHODS: Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort. RESULTS: A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Dose-limiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer). CONCLUSION: Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.
Anorexia ; Appointments and Schedules ; Breast Neoplasms ; Carcinoma, Non-Small-Cell Lung ; Cohort Studies ; Diarrhea ; Epithelial Cells ; Humans ; In Vitro Techniques ; Lung ; Maximum Tolerated Dose ; Pharmacokinetics ; Phosphotransferases ; Protein-Tyrosine Kinases* ; Pruritus ; Receptor, Epidermal Growth Factor ; Stomach Neoplasms ; Stomatitis ; Tyrosine*

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.
Alzheimer Disease ; Brain ; Brain Injury, Chronic* ; Cell Line ; Craniocerebral Trauma ; Gene Expression Profiling* ; Humans ; Models, Animal ; Neurodegenerative Diseases ; Phosphoprotein Phosphatases ; Phosphotransferases ; Sequence Analysis, RNA ; Tauopathies* ; Transcriptome*