T790M: revealing the secrets of a gatekeeper.

Non-small-cell lung cancers that harbor activating mutations in the gene represent an important molecularly defined subset of lung cancer. Despite dramatic initial responses with first- and second-generation EGFR-directed tyrosine-kinase inhibitors (TKIs) against these cancers, the development of a dominant and frequent resistance mechanism through a threonine-methionine amino acid substitution at position 790 (T790M) of has limited the long-term efficacy of these targeted therapies. This "gatekeeper" T790M alteration remains the only validated and relevant second-site resistance mutation for , allowing for focused research to understand and overcome T790M-mediated resistance.

Relationship between physician-adjudicated adverse events and patient-reported health-related quality of life in a phase II clinical trial (NCT01143402) of patients with metastatic uveal melanoma.

Purpose: Clinical trials commonly use physician-adjudicated adverse event (AE) assessment via the common terminology criteria for adverse events (CTCAE) for decision-making. Patient-reported health-related quality of life (HRQoL) data are becoming more frequent in oncology; however, the relationship between physician-adjudicated AE assessment and HRQoL is understudied.

Methods: Data from a phase II trial (clinicaltrials.

[The diagnosis and surgical procedure in calcified subtotal thrombosis of the left atrium in rheumatic heart defects].

The authors share their experience with surgical treatment of 5 patients. The methods of thrombectomy from the left auricle used in their work as well as prophylactics of recurrent thrombosis are thought to improve results of treatment of rheumatic heart disease.